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

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

Authors :
Kentaro Oh-hashi
Kazutoshi Kiuchi
Fumio Tsuji
Source :
Journal of Receptors and Signal Transduction. 32:22-28
Publication Year :
2011
Publisher :
Informa UK Limited, 2011.

Abstract

Interleukin (IL)-1β 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).We investigated the effects of an Akt inhibitor, a phosphatidylinositol 3-kinase (PI3K) inhibitor, and Akt RNAi knockdown on IL-1β-induced protein phosphorylation in HFLS to clarify the role of the PI3K/Akt signaling pathway in the phosphorylation of the inhibitor of κB (IκB)α and heat shock protein 27 (HSP27).A multiplex suspension array system was used for the detection of phosphorylated proteins.IL-1β induced biphasic phosphorylation of IκBα, with the first phase occurring 10 min after IL-1β 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.Modulation of different stages of the PI3K/Akt pathway may differentially affect the phosphorylation of IκBα and HSP27 in HFLS.

Details

ISSN :
15324281 and 10799893
Volume :
32
Database :
OpenAIRE
Journal :
Journal of Receptors and Signal Transduction
Accession number :
edsair.doi.dedup.....0d9b925d2682369b78227c8160fe908f
Full Text :
https://doi.org/10.3109/10799893.2011.641976