IL-1 alpha Up-Regulates IL-6 Expression in Bovine Granulosa Cells via MAPKs and NF-B-k Signaling Pathways

Background/Aims: 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-1 alpha on IL-6 expression in granulosa cells. Methods: IL-6 expression after IL-1 alpha with/without inhibitors treatment was analyzed by RT-qPCR and ELISA. The phosphorylation of proteins induced by IL-1 alpha was analyzed by western blot. The intracellular cAMP level was assayed by immunoassay kit. Results: IL-1 alpha 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 IkB proteins inhibitors, respectively. Moreover, the phosphorylation levels of Erk, c-Jun, p38 and IkB alpha proteins were significantly increased after IL-1 alpha treatment. In addition, we also found that IL-1 alpha not only reversed the cAMP attenuated IL-6 expression, but also increased IL-1 alpha mRNA expression in granulosa cells. Conclusion: The regulation of IL-1 alpha on IL-6 expression is mediated by activation of MAPKs and NF-B-k signaling pathways. Moreover, IL-1 alpha may regulate the ovulation-related genes expression in granulosa cells by an autocrine and/or paracrine manner. (C) 2017 The Author(s) Published by S. Karger AG, Basel