Differential contributions of protein kinase C isoforms in the regulation of group IIA secreted phospholipase A(2) expression in cytokine-stimulated rat fibroblasts

作者：Sugita Mizuki; Kuwata Hiroshi^*; Kudo Ichiro; Hara Shuntaro

来源：Biochimica et Biophysica Acta-Molecular and Cell Biology of Lipids, 2010, 1801(1): 70-76.

DOI：10.1016/j.bbalip.2009.09.013

• sPLA(2)-IIA
• PKC alpha
• PKC lambda/iota
• IL-1 beta

Protein kinase C (PKC) is a family of serine/threonine kinases involved in various signal transduction pathways. We investigated the roles of PKC in the regulation of group IIA secreted phospholipase A(2) (sPLA(2)-IIA) expression in cytokine-stimulated rat fibroblastic 3Y1 cells. Here we show that the induction of sPLA(2)-IIA by proinflammatory cytokines was under the control of both classical cPKC alpha and atypical aPKC lambda/iota pathways by using PKC inhibitors, a PKC activator, and PKC knockdowns. Treatment of 3Y1 cells with PKC selective inhibitors having broad specificity, such as chelerythrine chloride and GF109203X, blocked IL-1 beta/TNF alpha-dependent induction of sPLA(2)-IIA protein in a dose-dependent manner. Treatment with the PKC activator phorbol 12-myristate 13-acetate (PMA), which activates cPKC and novel nPKC isoforms, markedly attenuated the cytokine-dependent induction of sPLA(2)-IIA expression. In comparison, 24-h pretreatment with PMA, which down-regulates these PKC isoforms, markedly enhanced sPLA(2)-IIA expression. Results with short hairpin RNA (shRNA)-mediated knockdown of PKC isoforms revealed that the cytokine-induced sPLA(2)-IIA expression was markedly enhanced in cPKC alpha knockdown cells compared to those in replicate control cells. In contrast, knockdown of the aPKC lambda/iota, isoform reduced the cytokine-induced expression of sPLA(2)-IIA. These results suggest that the aPKC lambda/iota pathway is required for the induction of sPLA(2)-IIA expression and that the cPKCa pathway acts as a negative regulator of sPLA(2)-IIA expression in cytokine-stimulated rat fibroblasts.

• 出版日期2010-1