Differential effects of Akt pathway inhibitors on IL-1 beta-induced protein phosphorylation in human fibroblast-like synoviocytes

作者：Tsuji Fumio^*; Oh hashi Kentaro; Kiuchi Kazutoshi

来源：Journal of Receptors and Signal Transduction, 2012, 32(1): 22-28.

DOI：10.3109/10799893.2011.641976

• I kappa B alpha
• heat shock protein 27
• Akt inhibitor IV
• LY-294002
• RNAi

Context: Interleukin (IL)-1 beta activates various signal transduction pathways including p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and Akt in human fibroblast-like synoviocytes (HFLS). %26lt;br%26gt;Objective: We investigated the effects of an Akt inhibitor, a phosphatidylinositol 3-kinase (PI3K) inhibitor, and Akt RNAi knockdown on IL-1 beta-induced protein phosphorylation in HFLS to clarify the role of the PI3K/Akt signaling pathway in the phosphorylation of the inhibitor of kappa B (I kappa B)alpha and heat shock protein 27 (HSP27). %26lt;br%26gt;Materials and methods: A multiplex suspension array system was used for the detection of phosphorylated proteins. %26lt;br%26gt;Results: IL-1 beta induced biphasic phosphorylation of I kappa B alpha, with the first phase occurring 10 min after IL-1 beta stimulation, and this was augmented by treatment with Akt inhibitor IV. However, this phenomenon was not observed after treatment with LY-294002, a PI3K inhibitor. Furthermore, Akt inhibitor IV suppressed ERK2 phosphorylation, whereas LY-294002 and Akt RNAi had no effect. In contrast, Akt inhibitor IV, LY-294002, and Akt RNAi augmented HSP27 phosphorylation. %26lt;br%26gt;Discussion and conclusions: Modulation of different stages of the PI3K/Akt pathway may differentially affect the phosphorylation of I kappa B alpha and HSP27 in HFLS.

• 出版日期2012-2