|Year : 2019 | Volume
| Issue : 3 | Page : 177-184
Cyclooxygenase-2 and decidual immune cells
Si-Yao Ha1, Hui-Li Yang1, Zhen-Zhen Lai1, Lu-Yu Ruan1, Jia-Wei Shi1, Ming-Qing Li2
1 Laboratory for Reproductive Immunology, Institute of Obstetrics and Gynecology, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai 200080, China
2 Laboratory for Reproductive Immunology, Institute of Obstetrics and Gynecology, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai 200080; Laboratory for Reproductive Immunology, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai 200011; Laboratory for Reproductive Immunology, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, Shanghai 230032, China
|Date of Submission||11-Apr-2019|
|Date of Web Publication||27-Sep-2019|
Institute of Obstetrics and Gynecology, Hospital of Obstetrics and Gynecology, Fudan University, No. 1326, Pingliang Road, Shanghai 200080
Source of Support: None, Conflict of Interest: None
Cyclooxygenase-2 (COX-2) is a rate-limiting enzyme in arachidonic acid (AA) metabolism. COX-2 and its products (prostanoids) serve versatile biological functions during pregnancy. Numerous evidences demonstrate special reprogramming of COX-2-catalyzing AA metabolism in decidual immune cells (DICs), particularly in decidual macrophages, corresponding to special gestational phases. This review summarizes the reprogramming of COX-2-catalyzing AA metabolism in DICs as well as the immunoregulation of diverse COX-2-generating prostanoids in DICs during the different phases of gestation.
Keywords: Cyclooxygenase-2; Decidual Immune Cell; Metabolism; Pregnancy; Prostanoid
|How to cite this article:|
Ha SY, Yang HL, Lai ZZ, Ruan LY, Shi JW, Li MQ. Cyclooxygenase-2 and decidual immune cells. Reprod Dev Med 2019;3:177-84
| Introduction|| |
The emerging field of immunometabolism has substantially progressed in recent years and provided novel insights into distinct metabolic regulators and reprogramming pathways of immune cell populations under various immunological settings.,,, Nevertheless, studies regarding immunometabolic reprogramming in the field of reproduction–immunity are still sparse. A genetically distinct fetus poses an immunological challenge to a pregnant female. During gestation, intricate crosstalk occur at the maternal–fetal interface, such as the formation of a functional synapse between invading fetal extravillous trophoblast cells and the involvement of various maternal immune cell subsets, epigenetically modified decidual stromal cells (DSCs), and decidual mesenchymal stem cells (dMSCs) synergistically creating a tolerogenic niche to support semiallogeneic fetal development., Among these factors, decidual immune cells (DICs), mainly consisting of T cells (10%–20%), decidual natural killer cells (dNKs, 50%–70%), decidual macrophages (dMφs, approximately 20%), and decidual dendritic cells (dDCs), adapt their phenotypic and functional characteristics in response to the special tissue microenvironment in order to provide an immunoprivileged matrix essential for embryo implantation, remodeling of the maternal spiral arteries, placental development, and labor.,,,,,,
Cyclooxygenases (COXs), officially known as prostaglandin–endoperoxide synthase (PTGS), are rate-limiting enzymes responsible for prostanoid formation during arachidonic acid (AA) metabolism. In the past 30 years, several studies have highlighted the role of COX-2, a type of COX, in multiple pregnancy processes including ovulation,,, fertilization,,, implantation,,,,, and parturition.,,, Given that DICs have been implicated in these processes, this review summarizes the reprogramming of COX-2-catalyzing AA metabolism in DICs as well as the immunoregulation of diverse COX-2-generating prostanoids in DICs during the different phases of gestation.
| Cyclooxygenase-2|| |
There are three isozymes of COXs encoded by distinct genes: a constitutive COX-1, an inducible COX-2, and a splice variant of COX-1 termed COX-3, all of which differ in their regulation of expression and tissue distribution. COX-1 encoded by the “housekeeping” gene, PTGS-1, is a constitutive enzyme associated with the endoplasmic reticulum (ER), which regulates angiogenesis in endothelial cells, maintains tissue homeostasis, and promotes cell proliferation during tumor progression., COX-3 is encoded by the same gene as COX-1, with the difference that COX-3 retains an intron that is not retained in COX-1; however, it does not result in a functional protein in humans.
Monotopic membrane protein COX-2, which was discovered in the laboratory of Daniel Simmons in the 1990s, is encoded by the “rapid response” gene, PTGS-2, and isassociated with both the nuclear envelope and ER. COX-2 shares ~60% amino acid sequence identity and structural homology (rmsd <1.0 Š) with COX-1. As a homodimer, it contains two separate active sites: (1) a COX active site that catalyzes the oxygenation of polyunsaturated fatty acids to hydroperoxy endoperoxides and (2) a peroxidase active site that reduces the hydroperoxide to alcohol. COX-2 is primarily an inducible enzyme (constitutively expressed in key regions of the body such as the brain, lungs, thymus, gut, and kidneys) whose expression is activated in a variety of cells in response to cytokines, mitogens, and endotoxins., A direct feedback is also observed between COX-2 and its products. COX-2 is a rate-limiting enzyme that converts AA to prostaglandin endoperoxide H2 (PGH2). PGH2, an unstable reaction intermediate, is subsequently converted into either prostaglandins (PGs, such as PGD2, PGE2, PGF2a, and PGI2) or thromboxane A2 (TXA2) by the action of specific synthases., They are ubiquitously produced, usually each cell type generates one or two dominant products, and act as autocrine and paracrine lipid mediators to maintain local homeostasis in the body. Each prostanoid acts preferentially with its corresponding receptors, i.e., PGD2 receptors (DP and CRTH2), PGE2 receptors (EP1, EP2, EP3, and EP4), PGF2a receptor (FP), PGI2 receptor (IP), and TXA2 receptor (TP),, to activate inhibitory or stimulatory transmembrane G protein-coupled EP or the nuclear receptor, PPARβ.,, COX-2 has long been known to be a target for pain relief, inflammation treatment,,,,,, and the modulation of multiple procarcinogenic effects.,,,,
The 1990s was the first time when the targeted disruption of COX-2 in mice was demonstrated to result in multiple failures in female reproductive processes. Consequently, the role of COX-2 in ovulation,,, fertilization,,, implantation,,,,, and parturition ,,, has been studied extensively. In the reproductive system, COX-1, constitutively expressed in the decidual lining of the uterus, is involved in the homeostasis and survival of the fetus without modulation during gestation or labor,,, whereas COX-2 is located in the uterine surface epithelium at preimplantation and in the superficial and deep uterine glands and matrix, and presents a dynamic pattern along the course of gestation.,, In terms of DICs, COX-1-like immunoreactivity was observed in most cell types (with the strongest staining being observed in dMφs), whereas only dMφs and dDCs stained positively for COX-2.,,,,, Moreover, COX-2-generated PGs may participate in DIC recruitment  and alter the cytokine expression profiles of DICs. Data showed that after PGE2 analog administration, dMφ and neutrophil numbers were significantly increased, whereas dNK numbers remained unchanged in first-trimester decidua in humans. Furthermore, major changes occur during Th2/Th1 cytokine production at the maternal–fetal interface during pregnancy. In the uterine and placental tissues, Th2 cytokines, such as interleukin-4 (IL-4) or IL-10, are significantly increased while the production of Th1 cytokines, such as IL-2, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and granulocyte–macrophage colony-stimulating factor (GM-CSF), is decreased; however, pretreatment of DICs with PGE2 modulates IL-2 and GM-CSF production., Moreover, DSCs, trophoblasts, and dMSCs produce PGs, and fortunately, several PG receptors are expressed in DICs, thereby facilitating an intricate immune crosstalk between them. The following sections elucidate the role of COX-2 and its products in DICs with respect to the regulation of the phenotypic and functional characteristics of DICs, particularly focusing on its upstream and downstream signaling cascades.
| Cyclooxygenase-2 and Decidual Macrophages|| |
Nonpregnant endometria contain only a small amount of Mφ; however, the number increases during gestation, accounting for around 20%–30% of all decidual leukocytes.,, In the maternal–fetal interface, dMφs play an indispensable role in implantation, maternal–fetal tolerance, tissue and vascular remodeling, and parturition.,,,,,,, In general, macrophage (Mφ) functions are decided in response to microenvironmental signals that drive the acquisition of polarized programs, whose extremes can be simplified using the M1 and M2 dichotomy: M1, a classically activated Mφ that is microbicidal and inflammatory; and M2, an alternatively activated Mφ that is immunomodulatory and can induce tolerance and the resolution of inflammation., dMφs, which do not follow the conventional M1/M2 categorization, are implicated to be a heterogeneous population of Mφs with diverse phenotypes and functions that facilitate adaptive responses to the ever-changing environment.,, From an immunometabolic perspective, dMφs and peripheral monocytes (pMos) have distinct metabolic profiles, out of which COX-2-catalyzing AA metabolism takes a predominant position, exerting profound influence on modulating the phenotypes and biological functions of dMφs.
Pregnancy can be a proinflammatory or anti-inflammatory condition depending on the gestational stage, and COX-2-generated prostanoids appear to be indispensable in both the inflammatory and anti-inflammatory phases of pregnancy. During early pregnancy, dMφs shift toward the anti-inflammatory M2 polarization, which prevents fetus rejection and allows fetal growth until parturition. Numerous evidences have demonstrated that the proinflammatory lipid mediator PGE2 mediates the polarization of the M2 Mφs,,,,, suggesting the role of PGE2 in dMφ polarization during early pregnancy. Interestingly, PGE2 switches dMφs toward an immunosuppressive phenotype  and upregulates the production of the immunosuppressive cytokine IL-10 in dMφs.,
However, at the onset of the implantation period, dMφs are induced toward inflammatory M1 activation, switched to a mixed M1/M2 profile, and maintained in this mixed phenotype until the early phase of the second trimester. During this stage, some special pregnancy processes occur, including blastocyst implantation, trophoblast invasion, and angiogenesis, which creates a veritable “battleground” of invading, dying, and repairing cells. Naturally, inflammatory dMφs are required to secure the adequate repair of the uterine epithelium and removal of cellular debris. Likewise, parturition (another proinflammatory event) is preceded by an accumulation of M1-type dMφs in the uterus. Previous studies have shown that appropriate COX-2-induced inflammation is a crucial event for both implantation  and initiation of human parturition,,,, which otherwise lead to undesirable pregnancy outcomes.,,,,,,,, However, there are only a handful of studies regarding placenta-derived prostanoids modulating dMφ polarization under such circumstances. During implantation and parturition, dMφs participate via the reprogramming of COX-2-catalyzing AA metabolism and the secretion of diverse prostanoids,,,, thereby facilitating trophoblast invasion, angiogenesis, cervical ripening, and myometrial contraction.
Among all COX-2 products, PGE2 and TXA2 are two of the most dominant products in both peripheral Mφs and dMφs.,, However, only PGE2 concentrations suffer the regulation of special hypoxic conditions in the maternal–fetal interface. Physiological concentrations of progesterone  and pregnancy-specific glycoproteins  stimulate COX-2 activity in dMφs, thereby contributing to the generation of an immune environment compatible with successful pregnancy. PGE2, after binding to different EP receptors, can regulate the function of many cell types, including macrophages, dendritic cells, and T and B lymphocytes, leading to both pro- and anti-inflammatory effects. As a proinflammatory mediator, PGE2 contributes to the regulation of the cytokine expression profile in the uterus and modulation of T cell differentiation.,, On the other hand, PGE2 has also been demonstrated to exert anti-inflammatory actions on innate immune cells such as neutrophils, monocytes, and NK cells as well as on acquired immune cells such as Th1 cells. In the maternal–fetal interface, dMφ-derived PGE2 has been implicated to be a paracrine mediator because PGE2 exerts effects on trophoblastic outgrowth, immunosuppression of T cell alloreactivity,, and proliferation and cytolytic activity of dNKs., TXA2, an unstable AA metabolite, has also been shown to be involved in the modulation of acquired immunity, thereby inducing the chemokinesis of native T cells and impairing DC-T cell adhesion and DC-dependent proliferation of T cells. However, studies on the potential functions of dMφ-derived TXA2 are limited. PGD2, another product of COX-2 in dMφs, appears to function in both inflammatory and homeostatic capacities , and is associated with decidual Th2 cell recruitment and inhibition of DC migration to the deciduas.
Due to high plasticity, abnormal activation of inflammation upregulates COX-2 expression in dMφs and drives M1 dMφ polarization. Infection is one of the leading causes in this polarization process, usually resulting in preterm birth (PTB),,, stillbirth,, and adverse fetal outcomes.,, Data show that infection enhances COX-2 activity in both peripheral tissues , and the maternal–fetal interface., Outside the uterus, reprogramming of the prostanoid metabolism can occur upon cellular differentiation, i.e., while resting Mφs produce TXA2 under excessive PGE2 conditions, the ratio changes to favor PGE2 production after lipopolysaccharide (LPS) activation. Whether such patterns apply to dMφs needs to be further elucidated. A variety of pathogens, such as LPS,, influenza A virus, and Plasmodium, have been reported to upregulate COX-2 expression in dMφs. Notably, placental malaria is highly associated with COX-2 upregulation in dMφs, and an estimated 125 million pregnancies globally are at risk of malaria each year, which causes substantial maternal and infant morbidity/mortality.,,, Plasmodium upregulates the expression of the proinflammatory cytokine, COX-2. However, COX-2 inhibitors can interfere with prostanoid synthesis and modulate the outcome of the pregnancy. Apart from microorganisms, harmful environmental stimuli such as diethylhexyl phthalate, widely used as a plasticizer in polyvinyl chloride products, also activate the expression of COX-2 in dMφs.
However, some studies question the significance of reprogramming COX-2-catalyzing AA metabolism in dMφs because no difference was observed between dMφs and pMos in terms of PGE2 production. In addition, LPS induces dMφs to generate and release the proinflammatory molecules, TNF-α, transforming growth factor-β, and IL-1, but not PGE2. Moreover, COX-2 expression in the placenta was also reported to be unchanged after preeclampsia. Therefore, more evidences are required to clarify these controversies.
| Cyclooxygenase-2 and T Cells, Decidual Natural Killer Cells, and Decidual Dendritic Cells|| |
Although T cells and dNKs do not possess the ability to synthesize prostanoids, dDCs generate a small amount of prostanoids due to the sparse dDC population in the maternal–fetal interface. COX-2-generated prostanoids, particularly PGE2 and PGD2, play a pivotal role in regulating the proliferation, apoptosis, differentiation, and diverse biological functions of T cells, dNKs, and dDCs.
Numerous studies have indicated that PGE2 maintains maternal–fetal tolerance by inducing Th1 cell anergy toward the semiallogeneic fetus.,, Compared to Th1 cells, not only do Th2 cells provide an alternative and potentially less embryo-toxic differentiation state during pregnancy, but also Th2 cytokines have the ability to repress Th1 cell differentiation and function. Therefore, it is preferred if the maternal–fetal interface has a general Th2-bias toward T cell response in order to minimize the generation of Th1 cells. PGE2 interacts with a number of different specific receptors in T cells, some of which elevate the intracellular level of cAMP, thereby leading to anergy. PGE2 specifically interacts with the EP4 receptor and directly affects T cell differentiation by inhibiting the production of Th1 cytokines, including IL-2 and IFN-γ, without affecting the production of the Th2 cytokines, IL-4, IL-5, and IL-10. Besides, PGE2 primes naïve T cells in a dose-dependent fashion to produce high levels of IL-4, IL-10, and IL-13, and very low levels of IL-2, IFN-γ, TNF-α, and TNF-β. Similar to T cells, PGE2 also inhibits the proliferation, cytotoxicity, and IFN-γ production of dNKs,,,, which causes them (CD56+ and CD16−) to exhibit immunosuppressive properties. Downregulation of the surface expression of the γ-chain on NK cells may be a mechanism by which PGE2 mediates the suppression of IL-15-activated NK cell function., Recently, NKs with a phenotype of PTGS2/COX-2 (high) in endometriosis were reported to present impaired cytotoxic activity. Unfortunately, only a few studies on the reprogramming of COX-2-catalyzing AA metabolism in dNKs have been conducted so far. In terms of dDCs, PGE2 blocks DC differentiation,, which is particularly relevant as the presence of mature DCs in placental tissues may induce potentially harmful T cell responses.
PGD2, analogous to PGE2, contributes to successful pregnancies by moderating the Th1/Th2 balance and antigen presentation by DCs via its dual receptor (CRTH2 and DP) system. CRTH2 is an extremely reliable marker for detecting human Th2 and T cytotoxic type 2 (Tc2) cells. Interestingly, CRTH2-expressing T cells are reported to be significantly higher in number in the decidua (especially at the implantation site),, suggesting that Th2 and Tc2 cells are recruited into the maternal–fetal interface via PGD2 mediation.
At the maternal–fetal interface, crosstalk between DSCs, trophoblasts, dMSCs, and DICs serves the prerequisite for successful pregnancies; however, the involvement of DSCs, trophoblasts, and dMSCs complicates the COX-2-catalyzing AA metabolic process in DICs. Although dMφs and DSCs are the main sources of PG, the rate of prostanoid synthesis is higher in dMφs than DSCs. DSCs, trophoblasts,, and dMSCs , have been shown to stimulate COX-2 activity in dMφs. For example, data newly identified significant paracrine interactions between DSCs and dMφs in response to pathogen-associated molecular patterns (PAMP) and microbial immune stimulation, partially due to PGE2. PGE2 was also shown to modulate the inhibitory effect of DSCs with respect to the survival and functions of dNKs and dDCs. Moreover, dMSCs have been reported to secrete the soluble factor, PGE2, to inhibit IL-2-induced dNK proliferation.
| Concluding Remarks|| |
COX-2 and its products play a dual role in both the proinflammatory and anti-inflammatory processes during pregnancy, and abundant evidences indicate special reprogramming of the COX-2-catalyzing AA metabolism in dMφs corresponding to special gestational phases. In general, the uterus favors a semiallogeneic, fetus-friendly environment where prostanoids modulate the dMφ acquisition of immunosuppressive phenotypes and functions. Notably, a rigorously controlled inflammatory state is elicited during implantation and parturition through which COX-2 expression is significantly upregulated in dMφs, followed by prostanoid formation. In contrast, abnormal inflammation, such as those caused by infection, probably induces an uncontrolled COX-2-relevant inflammatory cytokine cascade in dMφs, resulting in undesirable pregnancy outcomes. Similar to the actions in dMφs, prostanoids (PGE2 and PGD2 in particular) serve lipid mediators, thereby regulating the phenotypes and biological functions of T cells, dNKs, and dDCs. Moreover, the involvement of DSCs, trophoblasts, and dMSCs complicates this crosstalk. Considering its versatile functions at maternal–fetal interface, COX-2-catalyzing AA metabolism in DICs may be a new therapeutic target for reproductive disorder and abnormal parturition, such as recurrent implantation failures, abnormal abortion, PTB, and so on.
Even now, the delicate regulatory mechanisms, especially those at the genetic and epigenetic levels, underlying the reprogramming of COX-2-catalyzing AA metabolism in dMφs remain largely unknown, let alone in dDCs and other DIC populations synthesizing prostanoids. With so much emphasis on PGE2, it is also important to note that information on other COX-2 products is also rather limited.
Financial support and sponsorship
This study was supported by the Major Research Program of the National Natural Science Foundation of China (No. 31970798, 31671200, 91542108, and 81471513), Shanghai Rising-Star Program (16QA1400800), Innovation-oriented Science and Technology Grant from NPFPC Key Laboratory of Reproduction Regulation (CX2017-2), and the Program for Zhuoxue of Fudan University, China.
Conflicts of interest
There are no conflicts of interest.
| References|| |
O'Neill LA, Kishton RJ, Rathmell J. A guide to immunometabolism for immunologists. Nat Rev Immunol 2016;16:553-65. doi: 10.1038/Nri.2016.70.
Bordon Y. Immunometabolism: Old drug, new trick. Nat Rev Immunol 2018;18:295. doi: 10.1038/Nri.2018.29.
Pearce EL, Poffenberger MC, Chang CH, Jones RG. Fueling immunity: Insights into metabolism and lymphocyte function. Science 2013;342:1242454. doi: 10.1126/Science.1242454.
Pearce EJ, Pearce EL. Immunometabolism in 2017: Driving immunity: All roads lead to metabolism. Nat Rev Immunol 2018;18:81-2. doi: 10.1038/Nri.2017.139.
Thiele K, Diao L, Arck PC. Immunometabolism, pregnancy, and nutrition. Semin Immunopathol 2018;40:157-74. doi: 10.1007/S00281-017-0660-Y.
Ander SE, Diamond MS, Coyne CB. Immune responses at the maternal-fetal interface. Sci Immunol 2019;4. pii: eaat6114. doi: 10.1126/Sciimmunol. Aat6114.
Arck PC, Hecher K. Fetomaternal immune cross-talk and its consequences for maternal and offspring's health. Nat Med 2013;19:548-56. doi: 10.1038/Nm.3160.
Abomaray FM, Al Jumah MA, Alsaad KO, Jawdat D, Al Khaldi A, AlAskar AS, et al.
Phenotypic and functional characterization of mesenchymal stem/Multipotent stromal cells from decidua basalis of human term placenta. Stem Cells Int 2016;2016:5184601. doi: 10.1155/2016/5184601.
Robertson SA, Care AS, Moldenhauer LM. Regulatory T cells in embryo implantation and the immune response to pregnancy. J Clin Invest 2018;128:4224-35. doi: 10.1172/JCI122182.
Schumacher A, Sharkey DJ, Robertson SA, Zenclussen AC. Immune cells at the fetomaternal interface: How the microenvironment modulates immune cells to foster fetal development. J Immunol 2018;201:325-34. doi: 10.4049/Jimmunol.1800058.
Hsu P, Nanan RK. Innate and adaptive immune interactions at the fetal-maternal interface in healthy human pregnancy and pre-eclampsia. Front Immunol 2014;5:125. doi: 10.3389/Fimmu.2014.00125.
Gellersen B, Brosens JJ. Cyclic decidualization of the human endometrium in reproductive health and failure. Endocr Rev 2014;35:851-905. doi: 10.1210/Er.2014-1045.
Erlebacher A. Immunology of the maternal-fetal interface. Annu Rev Immunol 2013;31:387-411. doi: 10.1146/Annurev-Immunol-032712-100003.
Zhou JZ, Way SS, Chen K. Immunology of the uterine and vaginal mucosae. Trends Immunol 2018;39:302-14. doi: 10.1016/J. It.2018.01.007.
Smith WL, Urade Y, Jakobsson PJ. Enzymes of the cyclooxygenase pathways of prostanoid biosynthesis. Chem Rev 2011;111:5821-65. doi: 10.1021/Cr2002992.
Choi Y, Wilson K, Hannon PR, Rosewell KL, Brännström M, Akin JW, et al.
Coordinated regulation among progesterone, prostaglandins, and EGF-like factors in human ovulatory follicles. J Clin Endocrinol Metab 2017;102:1971-82. doi: 10.1210/Jc.2016-3153.
Sirois J, Sayasith K, Brown KA, Stock AE, Bouchard N, Doré M. Cyclooxygenase-2 and its role in ovulation: A 2004 account. Hum Reprod Update 2004;10:373-85. doi: 10.1093/Humupd/Dmh032.
Duffy DM. Novel contraceptive targets to inhibit ovulation: The prostaglandin E2 pathway. Hum Reprod Update 2015;21:652-70. doi: 10.1093/Humupd/Dmv026.
Huang N, Wang C, Zhang N, Mao W, Liu B, Shen Y, et al.
Effect of estrogen on prostaglandin synthetase in bovine oviduct smooth muscle. Eur J Pharmacol 2018;818:287-93. doi: 10.1016/J. Ejphar.2017.10.058.
Popli P, Sirohi VK, Manohar M, Shukla V, Kaushal JB, Gupta K, et al.
Regulation of cyclooxygenase-2 expression in rat oviductal epithelial cells: Evidence for involvement of GPR30/Src kinase-mediated EGFR signaling. J Steroid Biochem Mol Biol 2015;154:130-41. doi: 10.1016/J. Jsbmb.2015.07.019.
Shukla V, Kaushal JB, Sankhwar P, Manohar M, Dwivedi A. Inhibition of TPPP3 attenuates β-catenin/NF-κB/COX-2 signaling in endometrial stromal cells and impairs decidualization. J Endocrinol 2019;240:417-29. doi: 10.1530/JOE-18-0459.
Li X, Ballantyne LL, Crawford MC, FitzGerald GA, Funk CD. Isoform-specific compensation of cyclooxygenase (Ptgs) genes during implantation and late-stage pregnancy. Sci Rep 2018;8:12097. doi: 10.1038/S41598-018-30636-X.
Ruan YC, Guo JH, Liu X, Zhang R, Tsang LL, Dong JD, et al.
Activation of the epithelial Na+ channel triggers prostaglandin E2
release and production required for embryo implantation. Nat Med 2012;18:1112-7. doi: 10.1038/Nm.2771.
Shah BH, Catt KJ. Roles of LPA3 and COX-2 in implantation. Trends Endocrinol Metab 2005;16:397-9. doi: 10.1016/J. Tem.2005.09.009.
Glance DG, Elder MG, Myatt L. The actions of prostaglandins and their interactions with angiotensin II in the isolated perfused human placental cotyledon. Br J Obstet Gynaecol 1986;93:488-94.
Sun X, Guo JH, Zhang D, Chen JJ, Lin WY, Huang Y, et al.
Activation of the epithelial sodium channel (ENaC) leads to cytokine profile shift to pro-inflammatory in labor. EMBO Mol Med 2018;10. pii: e8868. doi: 10.15252/Emmm.201808868.
Bérard A, Sheehy O, Girard S, Zhao JP, Bernatsky S. Risk of preterm birth following late pregnancy exposure to NSAIDs or COX-2 inhibitors. Pain 2018;159:948-55. doi: 10.1097/J. Pain.0000000000001163.
Yonetani N, Yamamoto R, Murata M, Nakajima E, Taguchi T, Ishii K, et al.
Prediction of time to delivery by transperineal ultrasound in second stage of labor. Ultrasound Obstet Gynecol 2017;49:246-51. doi: 10.1002/Uog.15944.
Alotaibi M, Arrowsmith S, Wray S. Hypoxia-induced force increase (HIFI) is a novel mechanism underlying the strengthening of labor contractions, produced by hypoxic stresses. Proc Natl Acad Sci U S A 2015;112:9763-8. doi: 10.1073/Pnas.1503497112.
Smith WL, DeWitt DL, Garavito RM. Cyclooxygenases: Structural, cellular, and molecular biology. Annu Rev Biochem 2000;69:145-82. doi: 10.1146/Annurev. Biochem.69.1.145.
Picot D, Loll PJ, Garavito RM. The X-ray crystal structure of the membrane protein prostaglandin H2 synthase-1. Nature 1994;367:243-9. doi: 10.1038/367243a0.
Chandrasekharan NV, Dai H, Roos KL, Evanson NK, Tomsik J, Elton TS, et al.
COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: Cloning, structure, and expression. Proc Natl Acad Sci U S A 2002;99:13926-31. doi: 10.1073/Pnas.162468699.
Xie WL, Chipman JG, Robertson DL, Erikson RL, Simmons DL. Expression of a mitogen-responsive gene encoding prostaglandin synthase is regulated by mRNA splicing. Proc Natl Acad Sci U S A 1991;88:2692-6. doi: 10.1073/pnas.88.7.2692.
Kurumbail RG, Stevens AM, Gierse JK, McDonald JJ, Stegeman RA, Pak JY, et al.
Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents. Nature 1996;384:644-8. doi: 10.1038/384644a0.
Kurumbail RG, Kiefer JR, Marnett LJ. Cyclooxygenase enzymes: Catalysis and inhibition. Curr Opin Struct Biol 2001;11:752-60.
Mitchell JA, Kirkby NS. Eicosanoids, prostacyclin and cyclooxygenase in the cardiovascular system. Br J Pharmacol 2019;176:1038-50. doi: 10.1111/Bph.14167.
Obermajer N, Muthuswamy R, Lesnock J, Edwards RP, Kalinski P. Positive feedback between PGE2 and COX2 redirects the differentiation of human dendritic cells toward stable myeloid-derived suppressor cells. Blood 2011;118:5498-505. doi: 10.1182/Blood-2011-07-365825.
Ricciotti E, FitzGerald GA. Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol 2011;31:986-1000. doi: 10.1161/ATVBAHA.110.207449.
Cha YI, Solnica-Krezel L, DuBois RN. Fishing for prostanoids: Deciphering the developmental functions of cyclooxygenase-derived prostaglandins. Dev Biol 2006;289:263-72. doi: 10.1016/J. Ydbio.2005.10.013.
Woodward DF, Jones RL, Narumiya S. International union of basic and clinical pharmacology. LXXXIII: Classification of prostanoid receptors, updating 15 years of progress. Pharmacol Rev 2011;63:471-538. doi: 10.1124/Pr.110.003517.
Narumiya S, Sugimoto Y, Ushikubi F. Prostanoid receptors: Structures, properties, and functions. Physiol Rev 1999;79:1193-226. doi: 10.1152/Physrev.19220.127.116.113.
Gandhi J, Khera L, Gaur N, Paul C, Kaul R. Role of modulator of inflammation cyclooxygenase-2 in gammaherpesvirus mediated tumorigenesis. Front Microbiol 2017;8:538. doi: 10.3389/Fmicb.2017.00538.
Qiu J, Shi Z, Jiang J. Cyclooxygenase-2 in glioblastoma multiforme. Drug Discov Today 2017;22:148-56. doi: 10.1016/J. Drudis.2016.09.017.
Qiu HY, Wang PF, Li Z, Ma JT, Wang XM, Yang YH, et al.
Synthesis of dihydropyrazole sulphonamide derivatives that act as anti-cancer agents through COX-2 inhibition. Pharmacol Res 2016;104:86-96. doi: 10.1016/J. Phrs.2015.12.025.
Nasry WH, Rodriguez-Lecompte JC, Martin CK. Role of COX-2/PGE2 mediated inflammation in oral squamous cell carcinoma. Cancers (Basel) 2018;10. pii: E348. doi: 10.3390/Cancers10100348.
Rumzhum NN, Ammit AJ. Cyclooxygenase 2: Its regulation, role and impact in airway inflammation. Clin Exp Allergy 2016;46:397-410. doi: 10.1111/Cea.12697.
Nakata K, Hanai T, Take Y, Osada T, Tsuchiya T, Shima D, et al.
Disease-modifying effects of COX-2 selective inhibitors and non-selective NSAIDs in osteoarthritis: A systematic review. Osteoarthritis Cartilage 2018;26:1263-73. doi: 10.1016/J. Joca.2018.05.021.
Hermanson DJ, Gamble-George JC, Marnett LJ, Patel S. Substrate-selective COX-2 inhibition as a novel strategy for therapeutic endocannabinoid augmentation. Trends Pharmacol Sci 2014;35:358-67. doi: 10.1016/J. Tips.2014.04.006.
Martínez-Colón GJ, Moore BB. Prostaglandin E2 as a regulator of immunity to pathogens. Pharmacol Ther 2018;185:135-46. doi: 10.1016/J. Pharmthera.2017.12.008.
Dannenberg AJ, Lippman SM, Mann JR, Subbaramaiah K, DuBois RN. Cyclooxygenase-2 and epidermal growth factor receptor: Pharmacologic targets for chemoprevention. J Clin Oncol 2005;23:254-66. doi: 10.1200/JCO.2005.09.112.
Hashemi Goradel N, Najafi M, Salehi E, Farhood B, Mortezaee K. Cyclooxygenase-2 in cancer: A review. J Cell Physiol 2019;234:5683-99. doi: 10.1002/Jcp.27411.
Ricon I, Hanalis-Miller T, Haldar R, Jacoby R, Ben-Eliyahu S. Perioperative biobehavioral interventions to prevent cancer recurrence through combined inhibition of beta-adrenergic and cyclooxygenase 2 signaling. Cancer 2019;125:45-56. doi: 10.1002/Cncr.31594.
Roos J, Grösch S, Werz O, Schröder P, Ziegler S, Fulda S, et al.
Regulation of tumorigenic wnt signaling by cyclooxygenase-2, 5-lipoxygenase and their pharmacological inhibitors: A basis for novel drugs targeting cancer cells? Pharmacol Ther 2016;157:43-64. doi: 10.1016/J. Pharmthera.2015.11.001.
Lim H, Paria BC, Das SK, Dinchuk JE, Langenbach R, Trzaskos JM, et al.
Multiple female reproductive failures in cyclooxygenase 2-deficient mice. Cell 1997;91:197-208. doi: 10.1016/s0092-8674(00)80402-x.
Slater D, Dennes W, Sawdy R, Allport V, Bennett P. Expression of cyclo-oxygenase types-1 and-2 in human fetal membranes throughout pregnancy. J Mol Endocrinol 1999;22:125-30.
Slater DM, Dennes WJ, Campa JS, Poston L, Bennett PR. Expression of cyclo-oxygenase types-1 and-2 in human myometrium throughout pregnancy. Mol Hum Reprod 1999;5:880-4. doi: 10.1093/molehr/5.9.880.
Gibb W, Sun M. Localization of prostaglandin H synthase type 2 protein and mRNA in term human fetal membranes and decidua. J Endocrinol 1996;150:497-503. doi: 10.1677/joe.0.1500497.
Costa MA. The endocannabinoid system: A novel player in human placentation. Reprod Toxicol 2016;61:58-67. doi: 10.1016/J. Reprotox.2016.03.002.
Phillips RJ, Fortier MA, López Bernal A. Prostaglandin pathway gene expression in human placenta, amnion and choriodecidua is differentially affected by preterm and term labour and by uterine inflammation. BMC Pregnancy Childbirth 2014;14:241. doi: 10.1186/1471-2393-14-241.
Gram A, Fox B, Büchler U, Boos A, Hoffmann B, Kowalewski MP. Canine placental prostaglandin E2 synthase: Expression, localization, and biological functions in providing substrates for prepartum PGF2alpha synthesis. Biol Reprod 2014;91:154. doi: 10.1095/Biolreprod.114.122929.
Tawfik OW, Hunt JS, Wood GW. Implication of prostaglandin E2 in soluble factor-mediated immune suppression by murine decidual cells. Am J Reprod Immunol Microbiol 1986;12:111-7.
Lala PK, Kennedy TG, Parhar RS. Suppression of lymphocyte alloreactivity by early gestational human decidua. II. Characterization of the suppressor mechanisms. Cell Immunol 1988;116:411-22. doi: 10.1016/0008-8749(88)90241-9.
Parhar RS, Kennedy TG, Lala PK. Suppression of lymphocyte alloreactivity by early gestational human decidua. I. Characterization of suppressor cells and suppressor molecules. Cell Immunol 1988;116:392-410. doi: 10.1016/0008-8749(88)90240-7.
Gustafsson C, Mjösberg J, Matussek A, Geffers R, Matthiesen L, Berg G, et al.
Gene expression profiling of human decidual macrophages: Evidence for immunosuppressive phenotype. PLoS One 2008;3:e2078. doi: 10.1371/Journal. Pone.0002078.
Wetzka B, Nüsing R, Charnock-Jones DS, Schäfer W, Zahradnik HP, Smith SK. Cyclooxygenase-1 and-2 in human placenta and placental bed after normal and pre-eclamptic pregnancies. Hum Reprod 1997;12:2313-20. doi: 10.1093/humrep/12.10.2313.
Meadows JW, Pitzer B, Brockman DE, Myatt L. Differential localization of prostaglandin E synthase isoforms in human placental cell types. Placenta 2004;25:259-65. doi: 10.1016/J. Placenta.2003.09.004.
Salleh N. Diverse roles of prostaglandins in blastocyst implantation. ScientificWorldJournal 2014;2014:968141. doi: 10.1155/2014/968141.
Critchley HO, Jones RL, Lea RG, Drudy TA, Kelly RW, Williams AR, et al.
Role of inflammatory mediators in human endometrium during progesterone withdrawal and early pregnancy. J Clin Endocrinol Metab 1999;84:240-8. doi: 10.1210/Jcem.84.1.5380.
Milne SA, Henderson TA, Kelly RW, Saunders PT, Baird DT, Critchley HO. Leukocyte populations and steroid receptor expression in human first-trimester decidua; regulation by antiprogestin and prostaglandin E analog. J Clin Endocrinol Metab 2005;90:4315-21. doi: 10.1210/Jc.2004-2338.
Emond V, Fortier MA, Murphy BD, Lambert RD. Prostaglandin E2 regulates both interleukin-2 and granulocyte-macrophage colony-stimulating factor gene expression in bovine lymphocytes. Biol Reprod 1998;58:143-51. doi: 10.1095/biolreprod58.1.143.
Fortin M, Ouellette MJ, Lambert RD. TGF-beta 2 and PGE2 in rabbit blastocoelic fluid can modulate GM-CSF production by human lymphocytes. Am J Reprod Immunol 1997;38:129-39.
Schatz F, Kayisli UA, Vatandaslar E, Ocak N, Guller S, Abrahams VM, et al.
Toll-like receptor 4 expression in decidual cells and interstitial trophoblasts across human pregnancy. Am J Reprod Immunol 2012;68:146-53. doi: 10.1111/J.1600-0897.2012.01148.X.
Bulmer JN, Morrison L, Longfellow M, Ritson A, Pace D. Granulated lymphocytes in human endometrium: Histochemical and immunohistochemical studies. Hum Reprod 1991;6:791-8. doi: 10.1093/oxfordjournals.humrep.a137430.
Bulmer JN, Morrison L, Smith JC. Expression of class II MHC gene products by macrophages in human uteroplacental tissue. Immunology 1988;63:707-14.
Lessin DL, Hunt JS, King CR, Wood GW. Antigen expression by cells near the maternal-fetal interface. Am J Reprod Immunol Microbiol 1988;16:1-7.
Wang XQ, Zhou WJ, Hou XX, Fu Q, Li DJ. Trophoblast-derived CXCL16 induces M2 macrophage polarization that in turn inactivates NK cells at the maternal-fetal interface. Cell Mol Immunol 2018;15:1038-46. doi: 10.1038/S41423-018-0019-X.
Dallagi A, Girouard J, Hamelin-Morrissette J, Dadzie R, Laurent L, Vaillancourt C, et al.
The activating effect of IFN-γ on monocytes/macrophages is regulated by the LIF-trophoblast-IL-10 axis via Stat1 inhibition and Stat3 activation. Cell Mol Immunol 2015;12:326-41. doi: 10.1038/Cmi.2014.50.
Helige C, Ahammer H, Moser G, Hammer A, Dohr G, Huppertz B, et al.
Distribution of decidual natural killer cells and macrophages in the neighbourhood of the trophoblast invasion front: A quantitative evaluation. Hum Reprod 2014;29:8-17. doi: 10.1093/Humrep/Det353.
Guenther S, Vrekoussis T, Heublein S, Bayer B, Anz D, Knabl J, et al.
Decidual macrophages are significantly increased in spontaneous miscarriages and over-express FasL: A potential role for macrophages in trophoblast apoptosis. Int J Mol Sci 2012;13:9069-80. doi: 10.3390/Ijms13079069.
Renaud SJ, Macdonald-Goodfellow SK, Graham CH. Coordinated regulation of human trophoblast invasiveness by macrophages and interleukin 10. Biol Reprod 2007;76:448-54. doi: 10.1095/Biolreprod.106.055376.
Ning F, Liu H, Lash GE. The role of decidual macrophages during normal and pathological pregnancy. Am J Reprod Immunol 2016;75:298-309. doi: 10.1111/Aji.12477.
Tang MX, Hu XH, Liu ZZ, Kwak-Kim J, Liao AH. What are the roles of macrophages and monocytes in human pregnancy? J Reprod Immunol 2015;112:73-80. doi: 10.1016/J. Jri.2015.08.001.
Svensson-Arvelund J, Ernerudh J. The role of macrophages in promoting and maintaining homeostasis at the fetal-maternal interface. Am J Reprod Immunol 2015;74:100-9. doi: 10.1111/Aji.12357.
Sica A, Erreni M, Allavena P, Porta C. Macrophage polarization in pathology. Cell Mol Life Sci 2015;72:4111-26. doi: 10.1007/S00018-015-1995-Y.
Mantovani A, Biswas SK, Galdiero MR, Sica A, Locati M. Macrophage plasticity and polarization in tissue repair and remodelling. J Pathol 2013;229:176-85. doi: 10.1002/Path.4133.
Jiang X, Du MR, Li M, Wang H. Three macrophage subsets are identified in the uterus during early human pregnancy. Cell Mol Immunol 2018;15:1027-37. doi: 10.1038/S41423-018-0008-0.
Zhang YH, He M, Wang Y, Liao AH. Modulators of the balance between M1 and M2 macrophages during pregnancy. Front Immunol 2017;8:120. doi: 10.3389/Fimmu.2017.00120.
Houser BL, Tilburgs T, Hill J, Nicotra ML, Strominger JL. Two unique human decidual macrophage populations. J Immunol 2011;186:2633-42. doi: 10.4049/Jimmunol.1003153.
Németh K, Leelahavanichkul A, Yuen PS, Mayer B, Parmelee A, Doi K, et al.
Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogramming of host macrophages to increase their interleukin-10 production. Nat Med 2009;15:42-9. doi: 10.1038/Nm.1905.
Larsson K, Kock A, Idborg H, Arsenian Henriksson M, Martinsson T, Johnsen JI, et al.
COX/mPGES-1/PGE2 pathway depicts an inflammatory-dependent high-risk neuroblastoma subset. Proc Natl Acad Sci U S A 2015;112:8070-5. doi: 10.1073/Pnas.1424355112.
Luan B, Yoon YS, Le Lay J, Kaestner KH, Hedrick S, Montminy M. CREB pathway links PGE2 signaling with macrophage polarization. Proc Natl Acad Sci U S A 2015;112:15642-7. doi: 10.1073/Pnas.1519644112.
Kim YG, Udayanga KG, Totsuka N, Weinberg JB, Núñez G, Shibuya A. Gut dysbiosis promotes M2 macrophage polarization and allergic airway inflammation via fungi-induced PGE2
. Cell Host Microbe 2014;15:95-102. doi: 10.1016/J. Chom.2013.12.010.
Zhang S, Liu Y, Zhang X, Zhu D, Qi X, Cao X, et al.
Prostaglandin E2 hydrogel improves cutaneous wound healing via M2 macrophages polarization. Theranostics 2018;8:5348-61. doi: 10.7150/Thno.27385.
Zhao G, Miao H, Li X, Chen S, Hu Y, Wang Z, et al.
TGF-β3-induced miR-494 inhibits macrophage polarization via suppressing PGE2 secretion in mesenchymal stem cells. FEBS Lett 2016;590:1602-13. doi: 10.1002/1873-3468.12200.
Demeure CE, Yang LP, Desjardins C, Raynauld P, Delespesse G. Prostaglandin E2 primes naive T cells for the production of anti-inflammatory cytokines. Eur J Immunol 1997;27:3526-31. doi: 10.1002/Eji.1830271254.
Ha CT, Waterhouse R, Wessells J, Wu JA, Dveksler GS. Binding of pregnancy-specific glycoprotein 17 to CD9 on macrophages induces secretion of IL-10, IL-6, PGE2, and TGF-beta1. J Leukoc Biol 2005;77:948-57. doi: 10.1189/Jlb.0804453.
Jaiswal MK, Mallers TM, Larsen B, Kwak-Kim J, Chaouat G, Gilman-Sachs A, et al.
V-ATPase upregulation during early pregnancy: A possible link to establishment of an inflammatory response during preimplantation period of pregnancy. Reproduction 2012;143:713-25. doi: 10.1530/REP-12-0036.
Mor G, Cardenas I, Abrahams V, Guller S. Inflammation and pregnancy: The role of the immune system at the implantation site. Ann N
Y Acad Sci 2011;1221:80-7. doi: 10.1111/J.1749-6632.2010.05938.X.
Hamilton S, Oomomian Y, Stephen G, Shynlova O, Tower CL, Garrod A, et al.
Macrophages infiltrate the human and rat decidua during term and preterm labor: Evidence that decidual inflammation precedes labor. Biol Reprod 2012;86:39. doi: 10.1095/Biolreprod.111.095505.
Kishore AH, Liang H, Kanchwala M, Xing C, Ganesh T, Akgul Y, et al.
Prostaglandin dehydrogenase is a target for successful induction of cervical ripening. Proc Natl Acad Sci U S A 2017;114:E6427-36. doi: 10.1073/Pnas.1704945114.
Kishore AH, Owens D, Word RA. Prostaglandin E2 regulates its own inactivating enzyme, 15-PGDH, by EP2 receptor-mediated cervical cell-specific mechanisms. J Clin Endocrinol Metab 2014;99:1006-18. doi: 10.1210/Jc.2013-3392.
Reese J, Paria BC, Brown N, Zhao X, Morrow JD, Dey SK. Coordinated regulation of fetal and maternal prostaglandins directs successful birth and postnatal adaptation in the mouse. Proc Natl Acad Sci U S A 2000;97:9759-64. doi: 10.1073/pnas.97.17.9759.
Timmons BC, Reese J, Socrate S, Ehinger N, Paria BC, Milne GL, et al.
Prostaglandins are essential for cervical ripening in LPS-mediated preterm birth but not term or antiprogestin-driven preterm ripening. Endocrinology 2014;155:287-98. doi: 10.1210/En.2013-1304.
Olson DM, Ammann C. Role of the prostaglandins in labour and prostaglandin receptor inhibitors in the prevention of preterm labour. Front Biosci 2007;12:1329-43.
Lee PR, Kim SR, Jung BK, Kim KR, Chung JY, Won HS, et al.
Therapeutic effect of cyclo-oxygenase inhibitors with different isoform selectivity in lipopolysaccharide-induced preterm birth in mice. Am J Obstet Gynecol 2003;189:261-6. doi: 10.1067/mob.2003.485.
Loudon JA, Groom KM, Bennett PR. Prostaglandin inhibitors in preterm labour. Best Pract Res Clin Obstet Gynaecol 2003;17:731-44.
Gross G, Imamura T, Vogt SK, Wozniak DF, Nelson DM, Sadovsky Y, et al.
Inhibition of cyclooxygenase-2 prevents inflammation-mediated preterm labor in the mouse. Am J Physiol Regul Integr Comp Physiol 2000;278:R1415-23. doi: 10.1152/Ajpregu.2000.278.6.R1415.
Hirota Y, Daikoku T, Tranguch S, Xie H, Bradshaw HB, Dey SK. Uterine-specific p53 deficiency confers premature uterine senescence and promotes preterm birth in mice. J Clin Invest 2010;120:803-15. doi: 10.1172/JCI40051.
Sykes L, MacIntyre DA, Teoh TG, Bennett PR. Anti-inflammatory prostaglandins for the prevention of preterm labour. Reproduction 2014;148:R29-40. doi: 10.1530/REP-13-0587.
Nagamatsu T, Schust DJ. The immunomodulatory roles of macrophages at the maternal-fetal interface. Reprod Sci 2010;17:209-18. doi: 10.1177/1933719109349962.
Norwitz ER, Starkey PM, López Bernal A, Turnbull AC. Identification by flow cytometry of the prostaglandin-producing cell populations of term human decidua. J Endocrinol 1991;131:327-34. doi: 10.1677/joe.0.1310327.
Casey ML, Cox SM, Beutler B, Milewich L, MacDonald PC. Cachectin/tumor necrosis factor-alpha formation in human decidua. Potential role of cytokines in infection-induced preterm labor. J Clin Invest 1989;83:430-6. doi: 10.1172/JCI113901.
Wetzka B, Clark DE, Charnock-Jones DS, Zahradnik HP, Smith SK. Isolation of macrophages (Hofbauer cells) from human term placenta and their prostaglandin E2 and thromboxane production. Hum Reprod 1997;12:847-52. doi: 10.1093/humrep/12.4.847.
Wetzka B, Clark DE, Charnock-Jones DS, Zahradnik HP, Smith SK. PGE2 and TXA2 production by isolated macrophages from human placenta. Adv Exp Med Biol 1997;433:403-6. doi: 10.1007/978-1-4899-1810-9_88.
Korte K, Marzusch K, Dietl J. The production of prostanoids and the identification of macrophages in human decidua vera tissue. Arch Gynecol Obstet 1993;252:149-54.
Yagel S, Hurwitz A, Rosenn B, Keizer N. Progesterone enhancement of prostaglandin E2 production by fetal placental macrophages. Am J Reprod Immunol Microbiol 1987;14:45-8.
Egan KM, Lawson JA, Fries S, Koller B, Rader DJ, Smyth EM, et al.
COX-2-derived prostacyclin confers atheroprotection on female mice. Science 2004;306:1954-7. doi: 10.1126/Science.1103333.
Yao C, Sakata D, Esaki Y, Li Y, Matsuoka T, Kuroiwa K, et al.
Prostaglandin E2-EP4 signaling promotes immune inflammation through Th1 cell differentiation and Th17 cell expansion. Nat Med 2009;15:633-40. doi: 10.1038/Nm.1968.
Zhou WJ, Yang HL, Shao J, Mei J, Chang KK, Zhu R, et al.
Anti-inflammatory cytokines in endometriosis. Cell Mol Life Sci 2019;76:2111-32. doi: 10.1007/S00018-019-03056-X.
Harris SG, Padilla J, Koumas L, Ray D, Phipps RP. Prostaglandins as modulators of immunity. Trends Immunol 2002;23:144-50.
Juneja SC, Pfeifer TL, Tang XM, Williams RS, Chegini N. Modulation of mouse sperm-egg interaction, early embryonic development and trophoblastic outgrowth by activated and unactivated macrophages. Endocrine 1995;3:69-79. doi: 10.1007/BF02917451.
Parhar RS, Yagel S, Lala PK. PGE2-mediated immunosuppression by first trimester human decidual cells blocks activation of maternal leukocytes in the decidua with potential anti-trophoblast activity. Cell Immunol 1989;120:61-74. doi: 10.1016/0008-8749(89)90174-3.
Yagel S, Palti Z, Gallily R. Prostaglandin E2-mediated suppression of human maternal lymphocyte alloreactivity by first-trimester fetal macrophages. Obstet Gynecol 1988;72:648-54.
Bergeron D, Ouellette MJ, Lambert RD. PGE2, but not TGF beta 2, in rabbit blastocoelic fluid regulates the cytotoxic activities of NK and LAK cells. J Reprod Immunol 1997;33:203-19.
Scodras JM, Parhar RS, Kennedy TG, Lala PK. Prostaglandin-mediated inactivation of natural killer cells in the murine decidua. Cell Immunol 1990;127:352-67. doi: 10.1016/0008-8749(90)90138-h.
Nakahata N. Thromboxane A2: Physiology/pathophysiology, cellular signal transduction and pharmacology. Pharmacol Ther 2008;118:18-35. doi: 10.1016/J. Pharmthera.2008.01.001.
Jowsey IR, Thomson AM, Flanagan JU, Murdock PR, Moore GB, Meyer DJ, et al.
Mammalian class sigma glutathione S-transferases: Catalytic properties and tissue-specific expression of human and rat GSH-dependent prostaglandin D2 synthases. Biochem J 2001;359:507-16. doi: 10.1042/0264-6021:3590507.
Murata T, Maehara T. Discovery of anti-inflammatory role of prostaglandin D2. J Vet Med Sci 2016;78:1643-7. doi: 10.1292/Jvms.16-0347.
Saito S, Tsuda H, Michimata T. Prostaglandin D2 and reproduction. Am J Reprod Immunol 2002;47:295-302.
Freitas AC, Bocking A, Hill JE, Money DM; VOGUE Research Group. Increased richness and diversity of the vaginal microbiota and spontaneous preterm birth. Microbiome 2018;6:117. doi: 10.1186/S40168-018-0502-8.
Shivakoti R, Gupte N, Kumar NP, Kulkarni V, Balasubramanian U, Bhosale R, et al.
Intestinal barrier dysfunction and microbial translocation in human immunodeficiency virus-infected pregnant women are associated with preterm birth. Clin Infect Dis 2018;67:1103-9. doi: 10.1093/Cid/Ciy253.
Romero R, Dey SK, Fisher SJ. Preterm labor: One syndrome, many causes. Science 2014;345:760-5. doi: 10.1126/Science.1251816.
GBD 2015 Mortality and Causes of Death Collaborators. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: A systematic analysis for the global burden of disease study 2015. Lancet 2016;388:1459-544. doi: 10.1016/S0140-6736(16)31575-6.
Goldenberg RL, McClure EM, Saleem S, Reddy UM. Infection-related stillbirths. Lancet 2010;375:1482-90. doi: 10.1016/S0140-6736(09)61712-8.
Dudley DM, Van Rompay KK, Coffey LL, Ardeshir A, Keesler RI, Bliss-Moreau E, et al.
Miscarriage and stillbirth following maternal zika virus infection in nonhuman primates. Nat Med 2018;24:1104-7. doi: 10.1038/S41591-018-0088-5.
Collins S, Ramsay M, Slack MP, Campbell H, Flynn S, Litt D, et al.
Risk of invasive Haemophilus influenzae
infection during pregnancy and association with adverse fetal outcomes. JAMA 2014;311:1125-32. doi: 10.1001/Jama.2014.1878.
ANZIC Influenza Investigators and Australasian Maternity Outcomes Surveillance System. Critical illness due to 2009 A/H1N1 influenza in pregnant and postpartum women: Population based cohort study. BMJ 2010;340:c1279. doi: 10.1136/Bmj.C1279.
O'Brien AJ, Fullerton JN, Massey KA, Auld G, Sewell G, James S, et al.
Immunosuppression in acutely decompensated cirrhosis is mediated by prostaglandin E2. Nat Med 2014;20:518-23. doi: 10.1038/Nm.3516.
Keelan JA, Khan S, Yosaatmadja F, Mitchell MD. Prevention of inflammatory activation of human gestational membranes in an ex vivo
model using a pharmacological NF-kappaB inhibitor. J Immunol 2009;183:5270-8. doi: 10.4049/Jimmunol.0802660.
Tilley SL, Coffman TM, Koller BH. Mixed messages: Modulation of inflammation and immune responses by prostaglandins and thromboxanes. J Clin Invest 2001;108:15-23. doi: 10.1172/JCI13416.
Kadam L, Gomez-Lopez N, Mial TN, Kohan-Ghadr HR, Drewlo S. Rosiglitazone regulates TLR4 and rescues HO-1 and NRF2 expression in myometrial and decidual macrophages in inflammation-induced preterm birth. Reprod Sci 2017;24:1590-9. doi: 10.1177/1933719117697128.
Furuya H, Taguchi A, Kawana K, Yamashita A, Inoue E, Yoshida M, et al.
Resveratrol protects against pathological preterm birth by suppression of macrophage-mediated inflammation. Reprod Sci 2015;22:1561-8. doi: 10.1177/1933719115589413.
Coulombe F, Jaworska J, Verway M, Tzelepis F, Massoud A, Gillard J, et al.
Targeted prostaglandin E2 inhibition enhances antiviral immunity through induction of type I interferon and apoptosis in macrophages. Immunity 2014;40:554-68. doi: 10.1016/J. Immuni.2014.02.013.
Sarr D, Aldebert D, Marrama L, Frealle E, Gaye A, Brahim HO, et al.
Chronic infection during placental malaria is associated with up-regulation of cycloxygenase-2. Malar J 2010;9:45. doi: 10.1186/1475-2875-9-45.
Dellicour S, Tatem AJ, Guerra CA, Snow RW, ter Kuile FO. Quantifying the number of pregnancies at risk of malaria in 2007: A demographic study. PLoS Med 2010;7:e1000221. doi: 10.1371/Journal. Pmed.1000221.
Moore KA, Simpson JA, Scoullar MJL, McGready R, Fowkes FJI. Quantification of the association between malaria in pregnancy and stillbirth: A systematic review and meta-analysis. Lancet Glob Health 2017;5:e1101-12. doi: 10.1016/S2214-109X(17)30340-6.
Walker PG, ter Kuile FO, Garske T, Menendez C, Ghani AC. Estimated risk of placental infection and low birthweight attributable to Plasmodium falciparum
malaria in Africa in 2010: A modelling study. Lancet Glob Health 2014;2:e460-7. doi: 10.1016/S2214-109X(14)70256-6.
Desai M, ter Kuile FO, Nosten F, McGready R, Asamoa K, Brabin B, et al.
Epidemiology and burden of malaria in pregnancy. Lancet Infect Dis 2007;7:93-104. doi: 10.1016/S1473-3099(07)70021-X.
Nosten F, McGready R, Simpson JA, Thwai KL, Balkan S, Cho T, et al.
Effects of Plasmodium vivax
malaria in pregnancy. Lancet 1999;354:546-9. doi: 10.1016/s0140-6736(98)09247-2.
Agudelo OM, Aristizabal BH, Yanow SK, Arango E, Carmona-Fonseca J, Maestre A. Submicroscopic infection of placenta by Plasmodium
produces Th1/Th2 cytokine imbalance, inflammation and hypoxia in women from North-West Colombia. Malar J 2014;13:122. doi: 10.1186/1475-2875-13-122.
Everts B, Währborg P, Hedner T. COX-2-specific inhibitors – The emergence of a new class of analgesic and anti-inflammatory drugs. Clin Rheumatol 2000;19:331-43.
Tetz LM, Aronoff DM, Loch-Caruso R. Mono-ethylhexyl phthalate stimulates prostaglandin secretion in human placental macrophages and THP-1 cells. Reprod Biol Endocrinol 2015;13:56. doi: 10.1186/S12958-015-0046-8.
Mizuno M, Aoki K, Kimbara T. Functions of macrophages in human decidual tissue in early pregnancy. Am J Reprod Immunol 1994;31:180-8.
Hunt JS, Soares MJ, Lei MG, Smith RN, Wheaton D, Atherton RA, et al.
Products of lipopolysaccharide-activated macrophages (tumor necrosis factor-alpha, transforming growth factor-beta) but not lipopolysaccharide modify DNA synthesis by rat trophoblast cells exhibiting the 80-kDa lipopolysaccharide-binding protein. J Immunol 1989;143:1606-13.
Kvirkvelia N, Vojnovic I, Warner TD, Athie-Morales V, Free P, Rayment N, et al.
Placentally derived prostaglandin E2 acts via the EP4 receptor to inhibit IL-2-dependent proliferation of CTLL-2 T cells. Clin Exp Immunol 2002;127:263-9. doi: 10.1046/j.1365-2249.2002.01718.x.
Papadogiannakis N, Johnsen SA, Olding LB. Strong prostaglandin associated suppression of the proliferation of human maternal lymphocytes by neonatal lymphocytes linked to T versus T cell interactions and differential PGE2 sensitivity. Clin Exp Immunol 1985;61:125-34.
Saito S, Nakashima A, Shima T, Ito M. Th1/Th2/Th17 and regulatory T-cell paradigm in pregnancy. Am J Reprod Immunol 2010;63:601-10.doi: 10.1111/J.1600-0897.2010.00852.X.
Croxatto D, Vacca P, Canegallo F, Conte R, Venturini PL, Moretta L, et al.
Stromal cells from human decidua exert a strong inhibitory effect on NK cell function and dendritic cell differentiation. PLoS One 2014;9:e89006. doi: 10.1371/Journal. Pone.0089006.
Joshi PC, Zhou X, Cuchens M, Jones Q. Prostaglandin E2 suppressed IL-15-mediated human NK cell function through down-regulation of common gamma-chain. J Immunol 2001;166:885-91. doi: 10.4049/jimmunol.166.2.885.
Mei J, Zhou WJ, Zhu XY, Lu H, Wu K, Yang HL, et al.
Suppression of autophagy and HCK signaling promotes PTGS2high FCGR3-NK cell differentiation triggered by ectopic endometrial stromal cells. Autophagy 2018;14:1376-97. doi: 10.1080/15548627.2018.1476809.
Tsuda H, Michimata T, Sakai M, Nagata K, Nakamura M, Saito S. A novel surface molecule of Th2-and Tc2-type cells, CRTH2 expression on human peripheral and decidual CD4+ and CD8+ T cells during the early stage of pregnancy. Clin Exp Immunol 2001;123:105-11. doi: 10.1046/j.1365-2249.2001.01422.x.
Michimata T, Sakai M, Miyazaki S, Ogasawara MS, Suzumori K, Aoki K, et al.
Decrease of T-helper 2 and T-cytotoxic 2 cells at implantation sites occurs in unexplained recurrent spontaneous abortion with normal chromosomal content. Hum Reprod 2003;18:1523-8. doi: 10.1093/humrep/deg280.
Michimata T, Tsuda H, Sakai M, Fujimura M, Nagata K, Nakamura M, et al.
Accumulation of CRTH2-positive T-helper 2 and T-cytotoxic 2 cells at implantation sites of human decidua in a prostaglandin D(2)-mediated manner. Mol Hum Reprod 2002;8:181-7. doi: 10.1093/molehr/8.2.181.
Ishihara O, Sullivan MH, Elder MG. Differences of metabolism of prostaglandin E2 and F2 alpha by decidual stromal cells and macrophages in culture. Eicosanoids 1991;4:203-7.
Kelly RW, Critchley HO. A T-helper-2 bias in decidua: The prostaglandin contribution of the macrophage and trophoblast. J Reprod Immunol 1997;33:181-7.
Dominguez-Lopez P, Diaz-Cueto L, Olivares A, Ulloa-Aguirre A, Arechavaleta-Velasco F. Differential effect of DDT, DDE, and DDD on COX-2 expression in the human trophoblast derived HTR-8/SVneo cells. J Biochem Mol Toxicol 2012;26:454-60. doi: 10.1002/Jbt.21444.
Chen CP, Tsai PS, Huang CJ. Antiinflammation effect of human placental multipotent mesenchymal stromal cells is mediated by prostaglandin E2 via a myeloid differentiation primary response gene 88-dependent pathway. Anesthesiology 2012;117:568-79. doi: 10.1097/ALN.0b013e31826150a9.
Rogers LM, Anders AP, Doster RS, Gill EA, Gnecco JS, Holley JM, et al.
Decidual stromal cell-derived PGE2 regulates macrophage responses to microbial threat. Am J Reprod Immunol 2018;80:e13032. doi: 10.1111/Aji.13032.
Spaggiari GM, Capobianco A, Abdelrazik H, Becchetti F, Mingari MC, Moretta L. Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and cytokine production: Role of indoleamine 2,3-dioxygenase and prostaglandin E2. Blood 2008;111:1327-33. doi: 10.1182/Blood-2007-02-074997.