Transactivation of Src, PDGF receptor, and Akt is involved in IL-1β-induced ICAM-1 expression in A549 cells

✍ Scribed by Chih-Chung Lin; Chiang-Wen Lee; Tzu-Hua Chu; Ching-Yi Cheng; Shue-Fen Luo; Li-Der Hsiao; Chuen-Mao Yang

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 521 KB
• Volume: 211
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.20987

✦ Synopsis

Abstract

In previous study, interleukin‐1β (IL‐1β) has been shown to induce ICAM‐1 expression through MAPKs and NF‐κB in A549 cells. In addition to these pathways, transactivation of non‐receptor tyrosine kinase (Src), PDGF receptors (PDGFRs), and phosphatidylinositol 3‐kinase (PI3K)/Akt has been implicated in the expression of inflammatory genes. Here, we further investigated whether these different mechanisms participating in IL‐1β‐induced ICAM‐1 expression in A549 cells. We initially observed that IL‐1β‐induced ICAM‐1 promoter activity was attenuated by the inhibitors of Src (PP1), PDGFR (AG1296), PI3‐K (LY294002 and wortmannin), and Akt (SH‐5), revealed by reporter gene assay, Western blotting, and RT‐PCR analyses. The involvement of Src and PI3‐K/Akt in IL‐1β‐induced ICAM‐1 expression was significantly attenuated by transfection of A549 cells with dominant negative plasmids of Src, p85 and Akt, respectively. Src, PDGFR, and PI3K/Akt mediated the effects of IL‐1β because pretreatment with PP1, AG1296, and wortmannin also abrogated IL‐1β‐stimulated Src, PDGFR, and Akt phosphorylation, respectively. Moreover, pretreatment with p300 inhibitor (curcumin) also blocked ICAM‐1 expression. We further confirmed that p300 was associated with ICAM‐1 promoter which was dynamically linked to histone H4 acetylation stimulated by IL‐1β, determined by chromatin immunoprecipitation assay. Association of p300 and histone‐H4 to ICAM‐1 promoter was inhibited by LY294002. Up‐regulation of ICAM‐1 enhanced the adhesion of neutrophils onto A549 cell monolayer exposed to IL‐1β, which was inhibited by PP1, AG1296, LY294002, wortmannin, and helenalin. These results suggested that Akt phosphorylation mediated through transactivation of Src/PDGFR promotes the transcriptional p300 activity and eventually leads to ICAM‐1 expression induced by IL‐1β. J. Cell. Physiol. 211: 771–780, 2007. © 2007 Wiley‐Liss, Inc.