title: The Role of Progesterone and a Novel Progesterone Receptor, Progesterone Receptor Membrane Component 1, in the Inflammatory Response of Fetal Membranes to Ureaplasma parvum Infection.
abstract: Ureaplasma parvum (U. parvum) is gaining recognition as an important pathogen for chorioamnionitis and preterm premature rupture of membranes. We aimed to investigate the roles of progesterone (P4) and a novel progesterone receptor, progesterone receptor membrane component 1 (PGRMC1), in the response of fetal membranes to U. parvum. Fetal membrane cells (amnion, chorion and decidua) were isolated and confirmed to be free of Mycoplasmataceae. Cells were treated with U. parvum (5x106 CFU), and adherence was quantified by qPCR. Amnion and chorion cells were transfected with scrambled siRNA or validated PGRMC1 siRNA for 72h. Cells were then treated with U. parvum for 4h with or without pretreatment with P4 (10-7 M) or ethanol for 1h. Interleukin-8 (IL-8), matrix metalloproteinase 9 (MMP9) and cyclooxygenase (COX-2) mRNA expression were quantified by qRT-PCR. Culture medium was harvested and analyzed for IL-8 and prostaglandin (PGE2) secretion by ELISA and MMP9 activity by zymography. U. parvum had a mean adherence of 15.0±0.6%, 16.9± 3.7% and 4.7±0.3% in cultured amnion, chorion and decidua cells, respectively. Exposure to U. parvum elicited significant inflammatory responses including induction of IL-8, COX-2, PGE2 and MMP9. A possible role of PGRMC1 was identified in the inhibition of U. parvum-stimulated COX-2 and MMP9 mRNA expression in chorion cells and MMP9 activity in amnion cells. On the other hand, it might enhance the U. parvum-stimulated IL-8 protein secretion in amnion cells. P4, mediated through PGRMC1, significantly inhibited U. Parvum-induced MMP9 mRNA and COX-2 mRNA expression in chorion cells. P4 appeared to attenuate U. parvum induced IL-8 mRNA expression in chorion cells, but this P4 effect might not mediated through PGRMC1. In summary, U. parvum preferentially adheres to and induces inflammatory responses in chorion and amnion cells. P4 and PGRMC1 appear to differentially modulate the inflammatory responses induced by U. parvum among amnion and chorion cells.
authors.affiliation: Department of Obstetrics and Gynecology, Duke University, Durham, North Carolina, United States of America.
authors.forename: Liping
authors.initials: L
authors.lastname: Feng
authors.affiliation: Department of Obstetrics and Gynecology, Duke University, Durham, North Carolina, United States of America.
authors.forename: Carla E
authors.initials: CE
authors.lastname: Ransom
authors.affiliation: Department of Obstetrics and Gynecology, Duke University, Durham, North Carolina, United States of America.
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Nazzal
authors.affiliation: Department of Anesthesiology, Duke University, Durham, North Carolina, United States of America.
authors.forename: Terrence K
authors.initials: TK
authors.lastname: Allen
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina, United States of America.
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Li
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina, United States of America.
authors.forename: Tracy
authors.initials: T
authors.lastname: Truong
authors.affiliation: Department of Obstetrics and Gynecology, Duke University, Durham, North Carolina, United States of America.
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Potts
authors.affiliation: Department of Pediatrics, Duke University, Durham, North Carolina, United States of America.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Seed
authors.affiliation: Department of Obstetrics and Gynecology, Duke University, Durham, North Carolina, United States of America.
authors.forename: Amy P
authors.initials: AP
authors.lastname: Murtha
mesh_terms: D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D005321:Extraembryonic Membranes / Q000378:metabolism* / Q000382:microbiology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000382:microbiology; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D011247:Pregnancy; D011374:Progesterone / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D014509:Ureaplasma; D016869:Ureaplasma Infections / Q000378:metabolism*
chemical_list: D016209:Interleukin-8; D008565:Membrane Proteins; C115296:PGRMC1 protein, human; D011980:Receptors, Progesterone; D011374:Progesterone; D051546:Cyclooxygenase 2; D020780:Matrix Metalloproteinase 9