title: Tumor necrosis factor (TNF)-α upregulates progesterone receptor-A by activating the NF-κB signaling pathway in human decidua after labor onset.
abstract: To date, the relationship between inflammatory cytokines and progesterone receptors (PRs) has been little studied, although both mediate the mechanism of parturition in human deciduas. Thus, the aim of study was to investigate the role of an inflammatory cytokine, tumor necrosis factor (TNF)-α, in regulating progesterone withdrawal in decidua at human parturition. TNF-α levels and PR isoforms were compared in intrauterine deciduas from women who were in labor (IL, n = 10) or who were not in labor (NIL, n = 10). Nuclear factor-kappaB (NF-κB) signaling and PR status were analyzed in NIL deciduas after TNF-α stimulation. Immunohistochemistry, western blotting, ELISA and reverse transcription-polymerase chain reaction (RT-PCR) were used to localize and quantitate protein and mRNA expression. TNF-α immunostaining, protein levels, PR-A/PR-B ratio and COX-2 level were significantly higher in IL deciduas (all P < 0.05). NF-κB was activated by TNF-α after 24 h stimulation in a dose-dependent manner, and was significantly inactivated by the NF-κB inhibitor panepoxydone, which was associated with decreased PR-A and COX-2 expression (P < 0.05) in not in labor deciduas. In conclusion, TNF-α may have an important role in regulating progesterone withdrawal in human decidua following labor onset.
authors: Department of Obstetrics and Gynaecology, Nanjing Medical University, Nanjing, China.
authors: Z Y
authors: ZY
authors: Jiang
authors: Y Y
authors: YY
authors: Guo
authors: H B
authors: HB
authors: Ren
authors: Y F
authors: YF
authors: Zou
authors: M S
authors: MS
authors: Fan
authors: Y
authors: Y
authors: Lv
authors: P
authors: P
authors: Han
authors: W
authors: W
authors: De
authors: L Z
authors: LZ
authors: Sun
mesh_terms: D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002585:Cesarean Section; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D003656:Decidua / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007743:Labor, Obstetric / Q000378:metabolism; D036801:Parturition; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D046509:Tissue Culture Techniques; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D011257:Pregnancy Proteins; D020033:Protein Isoforms; C498143:RELA protein, human; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C101118:progesterone receptor A; C097314:progesterone receptor B; C101349:panepoxydone; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human