Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2022, 166(3):267-273 | DOI: 10.5507/bp.2021.026
The anti-inflammatory role of placental Hofbauer cells is altered in patients with chorioamnionitis: Are CYP2C8 and soluble epoxide hydrolase involved in immunomodulation?
- Department of Histology and Embryology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic
Aims: Hofbauer cells (HBCs) are placental macrophages playing various roles during normal and complicated pregnancies, and of the latter, chorioamnionitis is the most frequent.
Methods: In placenta with chorioamnionitis, we examined immunohistochemical expression profiles of IL-1β, IL-10, and their potential regulators, CYP2C8 and soluble epoxide hydrolase (sEH), in Hofbauer cells and compared the results with our previously published data for normal placenta.
Results: We found that the expression profiles of the studied proteins in Hofbauer cells in chorioamnionitis differs from normal placenta. In chorioamnionitis, HBCs showed a moderate expression of IL-1β together with a weak expression of IL-10 and CYP2C8. Contrary to normal placenta, HBCs in chorioamnionitis express sEH. We demonstrated a moderate positive correlation between the expression of CYP2C8 and sEH in chorioamnionitis (Spearman r = 0.5654), suggesting enhanced degradation of anti-inflammatory epoxyeicosatrienoic acids. Moreover, the relations of IL-1β and IL-10 to CYP2C8, previously described in normal placenta, disappeared. Furthermore, a weak expression of anti-inflammatory IL-10 in chorioamnionitis was accompanied by change in circularity of HBCs (Spearman r = 0.8193).
Conclusion: Taken together, these findings suggest a possible alteration of the anti-inflammatory role of HBCs and its regulation in chorioamnionitis.
Keywords: placental macrophages, chorioamnionitis, pro- and anti-inflammatory cytokines, CYP epoxygenases
Received: January 21, 2021; Revised: April 20, 2021; Accepted: April 21, 2021; Prepublished online: May 11, 2021; Published: September 14, 2022 Show citation
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References
- 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(1):80-7.
Go to original source...
Go to PubMed...
- Fu B, Wei H. Decidual natural killer cells and the immune microenvironment at the maternal-fetal interface. Sci China Life Sci 2016;59(12):1224-31.
Go to original source...
Go to PubMed...
- Kim SY, Romero R, Tarca AL, Bhatti G, Kim CJ, Lee J, Elsey A, Than NG, Chaiworapongsa T, Hassan SS, Kang GH, Kim JS. Methylome of fetal and maternal monocytes and macrophages at the feto-maternal interface. Am J Reprod Immunol 2012;68(1):8-27.
Go to original source...
Go to PubMed...
- Bulmer JN, Johnson PM. Macrophage populations in the human placenta and amniochorion. Clin Exp Immunol 1984;57(2):393-403.
Go to PubMed...
- Böckle BC, Sölder E, Kind S, Romani N, Sepp NT. DC-sign+ CD163+ macrophages expressing hyaluronan receptor LYVE-1 are located within chorion villi of the placenta. Placenta 2008;29(2):187-92.
Go to original source...
Go to PubMed...
- Joerink M, Rindsjö E, van Riel B, Alm J, Papadogiannakis N. Placental macrophage (Hofbauer cell) polarization is independent of maternal allergen-sensitization and presence of chorioamnionitis. Placenta 2011;32(5):380-5.
Go to original source...
Go to PubMed...
- Martinez FO, Sica A, Mantovani A, Locati M. Macrophage activation and polarization. Front Biosci 2008;13:453-61.
Go to original source...
Go to PubMed...
- Svensson J, Jenmalm MC, Matussek A, Geffers R, Berg G, Ernerudh J. Macrophages at the fetal-maternal interface express markers of alternative activation and are induced by M-CSF and IL-10. J Immunol 2011;187(7):3671-82.
Go to original source...
Go to PubMed...
- Swieboda D, Johnson EL, Beaver J, Haddad L, Enninga EAL, Hathcock M, Cordes S, Jean V, Lane I, Skountzou I, Chakraborty R. Baby's First Macrophage: Temporal Regulation of Hofbauer Cell Phenotype Influences Ligand-Mediated Innate Immune Responses across Gestation. J Immunol 2020; 204(9):2380-91.
Go to original source...
Go to PubMed...
- Tauber Z, Foltynkova T, Cizkova K. Morphometric analysis of Hofbauer cells in normal placenta and chorioamnionitis in humans. Anat Histol Embryol 2021;50(2):396-403.
Go to original source...
Go to PubMed...
- Yao Y, Xu XH, Jin L. Macrophage Polarization in Physiological and Pathological Pregnancy. Front Immunol 2019;10:792.
Go to original source...
Go to PubMed...
- Reyes L, Golos TG. Hofbauer Cells: Their Role in Healthy and Complicated Pregnancy. Front Immunol 2018;9:2628.
Go to original source...
Go to PubMed...
- Tauber Z, Chroma K, Baranova R, Cizkova K. The expression patterns of IL-1β and IL-10 and their relation to CYP epoxygenases in normal human placenta. Ann Anat 2021 [Epub ahead of print] doi: 10.1016/j.aanat.2020.151671
Go to original source...
Go to PubMed...
- Seval Y, Korgun ET, Demir R. Hofbauer cells in early human placenta: possible implications in vasculogenesis and angiogenesis. Placenta 2007;28(8-9):841-5.
Go to original source...
Go to PubMed...
- Loegl J, Hiden U, Nussbaumer E, Schliefsteiner C, Cvitic S, Lang I, Wadsack C, Huppertz B, Desoye G. Hofbauer cells of M2a, M2b and M2c polarization may regulate feto-placental angiogenesis. Reproduction 2016;152(5):447-55.
Go to original source...
Go to PubMed...
- Ben Amara A, Gorvel L, Baulan K, Derain-Court J, Buffat C, Vérollet C, Textoris J, Ghigo E, Bretelle F, Maridonneau-Parini I, Mege JL. Placental macrophages are impaired in chorioamnionitis, an infectious pathology of the placenta. J Immunol 2013;191(11):5501-14.
Go to original source...
Go to PubMed...
- Schliefsteiner C, Peinhaupt M, Kopp S, Lögl J, Lang-Olip I, Hiden U, Heinemann A, Desoye G, Wadsack C. Human Placental Hofbauer Cells Maintain an Anti-inflammatory M2 Phenotype despite the Presence of Gestational Diabetes Mellitus. Front Immunol 2017;8:888.
Go to original source...
Go to PubMed...
- Sisino G, Bouckenooghe T, Aurientis S, Fontaine P, Storme L, Vambergue A. Diabetes during pregnancy influences Hofbauer cells, a subtype of placental macrophages, to acquire a pro-inflammatory phenotype. Biochim Biophys Acta 2013;1832(12):1959-68.
Go to original source...
Go to PubMed...
- Tamblyn JA, Lissauer DM, Powell R, Cox P, Kilby MD. The immunological basis of villitis of unknown etiology - review. Placenta 2013;34(10):846-55.
Go to original source...
Go to PubMed...
- Tang Z, Buhimschi IA, Buhimschi CS, Tadesse S, Norwitz E, Niven-Fairchild T, Huang ST, Guller S. Decreased levels of folate receptor-β and reduced numbers of fetal macrophages (Hofbauer cells) in placentas from pregnancies with severe pre-eclampsia. Am J Reprod Immunol 2013;70(2):104-15.
Go to original source...
Go to PubMed...
- Mueller-Heubach E, Rubinstein DN, Schwarz SS. Histologic chorioamnionitis and preterm delivery in different patient populations. Obstet Gynecol 1990;75(4):622-6.
Go to PubMed...
- Dammann O, Leviton A. Maternal Intrauterine Infection, Cytokines, and Brain Damage in the Preterm Newborn. Pediatr Res 1997;42(1):1-8.
Go to original source...
Go to PubMed...
- Gaudet LM, Smith GN. Cerebral palsy and chorioamnionitis: the inflammatory cytokine link. Obstet Gynecol Surv 2001;56(7):433-6.
Go to original source...
Go to PubMed...
- Ramsey PS, Lieman JM, Brumfield CG, Carlo W. Chorioamnionitis increases neonatal morbidity in pregnancies complicated by preterm premature rupture of membranes. Am J Obstet Gynecol 2005;192(4):1162-6.
Go to original source...
Go to PubMed...
- Spector AA, Fang X, Snyder GD, Weintraub NL. Epoxyeicosatrienoic acids (EETs): metabolism and biochemical function. Prog Lipid Res 2004;43(1):55-90.
Go to original source...
Go to PubMed...
- Panigrahy D, Kalish BT, Huang S, Bielenberg DR, Le HD, Yang J, Edin ML, Lee CR, Benny O, Mudge DK, Butterfield CE, Mammoto A, Mammoto T, Inceoflu B, Jenkins RL, Simpson MA, Akino T, Lih FB, Tomer KB, Ingber DE, Hammock BD, Falck JR, Manthati VL, Kaipainen A, D´Amore PA, Puder M, Zeldin DC, Kieran MW. Epoxyeicosanoids promote organ and tissue regeneration. Roc Natl Acad Sci U S A 2013;110(33):13528-33.
Go to original source...
Go to PubMed...
- Thomson SJ, Askari A, Bishop-Bailey D. Anti-iflammatory effects of epoxyeicosatrienoic acids. Int J Vasc Med 2012;2012:605101.
Go to original source...
Go to PubMed...
- Bystrom J, Wray JA, Sugden MC, Holness MJ, Swales KE, Warner TD, Edin ML, Zeldin DC, Gilroy DW, Bishop-Bailey D. Endogenous epoxygenases are modulators of monocyte/macrophage activity. PLoS One 2011;6(10):e26591.
Go to original source...
Go to PubMed...
- Cizkova K, Tauber Z. Time-dependent expression pattern of cytochrome P450 epoxygenases and soluble epoxide hydrolase in normal human placenta. Acta Histochem 2018;120(6):513-9.
Go to original source...
Go to PubMed...
- Pineda-Torres M, Flores-Espinosa P, Espejel-Nunez A, Estrada-Gutierrez G, Flores-Pliego A, Maida-Claros R, Zaga-Clavellina V. Evidence of an immunosuppressive effect of progesterone upon in vitro secretion of proinflammatory and prodegradative factors in a model of choriodecidual infection. BJOG 2015;122(13):1798-807.
Go to original source...
Go to PubMed...
- Døllner H, Vatten L, Halgunset J, Rahimipoor S, Austgulen R. Histologic chorioamnionitis and umbilical serum levels of pro-inflammatory cytokines and cytokine inhibitors. BJOG 2002;109(5):534-9.
Go to original source...
Go to PubMed...
- Chatterjee P, Chiasson VL, Bounds KR, Mitchell BM. Regulation of the Anti-Inflammatory Cytokines Interleukin-4 and Interleukin-10 during Pregnancy. Front Immunol 2014;5:253.
Go to original source...
Go to PubMed...
- Puchner K, Iavazzo C, Gourgiotis D, Boutsikou M, Baka S, Hassiakos D, Kouskouni E, Economou E, Malamitsi-Puchner A, Creatsas G. Mid-trimester amniotic fluid interleukins (IL-1beta, IL-10 and IL-18) as possible predictors of preterm delivery. In vivo 2011;25(1):141-8.
Go to PubMed...
- Girard S, Tremblay L, Lepage M, Sébire G. IL-1 receptor antagonist protects against placental and neurodevelopmental defects induced by maternal inflammation. J Immunol 2010;184(7):3997-4005.
Go to original source...
Go to PubMed...
- Hung TH, Chen SF, Hsu JJ, Hsieh CC, Hsueh S, Hsieh TT. Tumour necrosis factor-alpha converting enzyme in human gestational tissues from pregnancies complicated by chorioamnionitis. Placenta 2006;27(9-10):996-1006.
Go to original source...
Go to PubMed...
- Mitra R, Guo Z, Milani M, Mesaros C, Rodriguez M, Nguyen J, Luo X, Clarke D, Lamba J, Schuetz E, Donner DB, Puli N, Falck JR, Capdevila J, Gupta K, Blair IA, Potter DA. CYP3A4 mediates growth of estrogen receptor-positive breast cancer cells in part by inducing nuclear translocation of phospho-Stat3 through biosynthesis of (+/-)-14,15-epoxyeicosatrienoic acid (EET). J Biol Chem 2011;286(20):17543-59.
Go to original source...
Go to PubMed...
- Williams L, Bradley L, Smith A, Foxwell B. Signal transducer and activator of transcription 3 is the dominant mediator of the anti-inflammatory effects of IL-10 in human macrophages. J Immunol 2004;172(1):567-76.
Go to original source...
Go to PubMed...
- Zeldin DC. Epoxygenase pathways of arachidonic acid metabolism. J Biol Chem 2001;276(39):36059-62.
Go to original source...
Go to PubMed...
- Eligini S, Crisci M, Bono E, Songia P, Tremoli E, Colombo GI, Colli S. Human monocyte-derived macrophages spontaneously differentiated in vitro show distinct phenotypes. J Cell Physiol 2013;228(7):1464-72.
Go to original source...
Go to PubMed...
- Schliefsteiner C, Ibesich S, Wadsack C. Placental Hofbauer Cell Polarization Resists Inflammatory Cues In Vitro. Int J Mol Sci 2020;21(3):736.
Go to original source...
Go to PubMed...
- Porcheray F, Viaud S, Rimaniol AC, Léone C, Samah B, Dereuddre-Bosquet N, Dormont D, Gras G. Macrophage activation switching: an asset for the resolution of inflammation. Clin Exp Immunol 2005;142(3):481-9.
Go to original source...
Go to PubMed...
- Vogel DY, Glim JE, Stavenuiter AW, Breur M, Heijnen P, Amor S, Dijkstra CD, Beelen RHJ. Human macrophage polarization in vitro: maturation and activation methods compared. Immunobiology 2014;219(9):695-703.
Go to original source...
Go to PubMed...
- Tedesco S, Bolego C, Toniolo A, Nassi A, Fadini GP, Locati M, Cignarella A. Phenotypic activation and pharmacological outcomes of spontaneously differentiated human monocyte-derived macrophages. Immunobiology 2015;220(5):545-54.
Go to original source...
Go to PubMed...
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