title: hCG Secretion in human choriocarcinoma JAR cells is MAPK but not Stat3 dependent: contributions of TNFalpha and IL-1beta to inflammation-induced hCG secretion.
abstract: Inflammatory mediators play critical physiologic roles throughout the course of normal pregnancy. At the same time, uncontrolled inflammation appears to have an adverse affect on pregnancy outcome. Thus, a crucial task of reproductive immunology is to define the mechanisms through which inflammation is controlled at the maternal-fetal interface. We examined the signaling pathways activated in the human choriocarcinoma cell line, JAR, in response to an in vitro model of an inflammatory challenge. We incubated JAR cells with medium from peripheral blood mononuclear cells (PBMC) that had been activated with either LPS or PHA. Conditioned medium from each experimental model induced MAP kinase and Stat3 phosphorylation as well as human chorionic gonadotropin (hCG) secretion from JAR cells. hCG secretion could be blocked by pharmacologic inhibition of MAP kinase but not by inhibition of Stat3 using an siRNA approach. The MAPK activators IL-1beta and TNFalpha both induced hCG secretion from JAR cells, but not the Stat3 activators IFN-gamma and IL-6. Furthermore, hCG secretion induced by conditioned media could be blocked by IL-1 receptor antagonist. We conclude that inflammation at the maternal-fetal interface may involve complex webs of regulatory and counter-regulatory mechanisms that involve multiple cytokines and at least two major, independent cell-signaling systems.
authors.affiliation: Department of Pediatrics, University of Oklahoma College of Medicine, Oklahoma City, 73014, USA.
authors.forename: K
authors.initials: K
authors.lastname: Jiang
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: J N
authors.initials: JN
authors.lastname: Jarvis
mesh_terms: D045744:Cell Line, Tumor; D002822:Choriocarcinoma; D006063:Chorionic Gonadotropin / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008954:Models, Biological; D010766:Phosphorylation; D011247:Pregnancy; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014594:Uterine Neoplasms
chemical_list: D006063:Chorionic Gonadotropin; D017077:Culture Media, Conditioned; D007375:Interleukin-1; D008070:Lipopolysaccharides; D034741:RNA, Small Interfering; D017472:Receptors, Interleukin-1; D050796:STAT3 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; D020929:Mitogen-Activated Protein Kinase Kinases