title: IL-1α Up-Regulates IL-6 Expression in Bovine Granulosa Cells via MAPKs and NF-κB Signaling Pathways.
abstract: OBJECTIVE
  IL-6 is one of the main cytokines in regulating ovarian follicular development and ovulation. However, the factors that regulate IL-6 expression in follicles are still unclear. The aim of this study was to elucidate the mechanisms underlying the effect of IL-1α on IL-6 expression in granulosa cells.
  
  
  METHODS
  IL-6 expression after IL-1α with/without inhibitors treatment was analyzed by RT-qPCR and ELISA. The phosphorylation of proteins induced by IL-1α was analyzed by western blot. The intracellular cAMP level was assayed by immunoassay kit.
  
  
  RESULTS
  IL-1α has a dose-dependent effect on IL-6 expression in granulosa cells. This promoting effect can be significantly attenuated by Erk, c-Jun, p38 and IκB proteins inhibitors, respectively. Moreover, the phosphorylation levels of Erk, c-Jun, p38 and IκBα proteins were significantly increased after IL-1α treatment. In addition, we also found that IL-1α not only reversed the cAMP attenuated IL-6 expression， but also increased IL-1α mRNA expression in granulosa cells.
  
  
  CONCLUSIONS
  The regulation of IL-1α on IL-6 expression is mediated by activation of MAPKs and NF-κB signaling pathways. Moreover，IL-1α may regulate the ovulation-related genes expression in granulosa cells by an autocrine and/or paracrine manner.
authors.forename: Meng
authors.initials: M
authors.lastname: Yang
authors.forename: Xurong
authors.initials: X
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Xuezhi
authors.initials: X
authors.lastname: Wang
authors.forename: Jianxi
authors.initials: J
authors.lastname: Li
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006107:Granulosa Cells / Q000166:cytology / Q000378:metabolism; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology*; D015850:Interleukin-6 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D000242:Cyclic AMP; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Granulosa cells; IL-1α; IL-6; MAPKs pathway; NF-κB pathway