- 作者: B.S. Wung; C.W. Ni; D.L. Wang
- 作者服務機構: 1 Department of Applied Microbiology, National Chiayi University, Chiayi, Taiwan; ; 2 Institute of Biomedical Sciences, Cardiovascular Division, Academia Sinica, Taipei, Taiwan
- 中文摘要: --
- 英文摘要: Atherogenesis is a chronic inflammatory response and intercellular adhesion molecule (ICAM-1) induced by cytokines plays a role in this event. In this study, the molecular mechanisms of tumor neurosis factor α (TNFα)- and IL-6-induced ICAM-1 gene expression in endothelial cells (ECs) were examined. ECs infected with adenovirus carrying the dominant negative mutant of Rac (Ad-RacN17) exhibited inhibition in both TNFα- and IL-6-induced ICAM-1 expression. Consistently, ECs transfected with RacN17 inhibited both TNFα- and IL-6-induced ICAM-1 promoter activities. Functional analysis of ICAM-1 promoter, however, indicated that the cis-acting elements in response to TNFot and IL-6 are different. The NFκB binding site in the ICAM-1 promoter region was crucial for TNFoc-induced ICAM-1 expression but not for the induction by IL-6. ECs infected with Ad-RacN17 attenuated the TNFα-induced NFκB binding activity. In contrast, IL-6 activated a transcriptional factor, signal transducer and activator of transcription-3 (Stat3) via the phosphorylation of Tyr705 at Stat3. ECs transfected with the dominant negative mutant of Stat3 (Stat3F) demonstrated that Stat3 was required for IL-6-induced ICAM-1 gene expression. Interestingly, the phosphorylation of Tyr705 and Ser727 in Stat3 was greatly inhibited in IL-6-treated ECs previously infected with Ad-RacN17. Our data strongly indicated that ICAM-1 gene induction by TNFα and IL-6 is mediated mainly via NFκB and Stat3, respectively and Racl appears to play a central role in modulating cytokine-induced ICAM-1 expression in ECs.
- 中文關鍵字: --
- 英文關鍵字: endothelial cells, IL-6, intercellular adhesion molecule-1, Rac, TNFα