Interleukin-8 induces the endothelial cell migration through the Rac1/RhoA-p38MAPK pathway

Y. Lai, X.H. Liu, Y. Zeng, Y. Zhang*, Y. Shen, Y.F. Liu*

Institute of Biomedical Engineering, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu (China)

*Laboratory of Biomedical Ultrasonics, West China Second University Hospital, Sichuan University, Chengdu (China)

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• Oncology

BACKGROUND AND OBJECTIVES: Endothelial cell migration is essential for tumor angiogenesis, and Interleukin-8 (IL-8) has been shown to play an important role in tumor growth, angiogenesis, and metastasis. The objective of this study was to investigate the molecular mechanism of IL-8 induced endothelial cell migration in vitro.

MATERIALS AND METHODS: Fluorescence microscope was used to study the distribution of cytoskeleton. The expression of Rac1 and RhoA protein was detected by western blotting. After endothelial cells were transfected by lipofectamine 2000 reagent, the Transwell chamber motility assay was applied to observe the migration of endothelial cells induced by IL-8. The active p38MAPK (mitogen-activated protein kinase) was evaluated by the p38MAPK activation assay.

RESULTS: We demonstrated that IL-8 activated cell migration can be impaired by p38MAPK inhibitor, suggesting the participation of p38MAPK in the cell migration. Our results indicated that p38MAPK signaling is required for membrane ruffles, lamellipodia extensions, and actin stress fibers formation induced by IL-8. Furthermore, p38MAPK inhibitor led to increased Rac1 and RhoA expression in IL-8 treated EA.hy926 cells. In addition, IL-8 induced p38MAPK activation was suppressed by dominant-negative mutant for Rac1 and RhoA.

CONCLUSIONS: Our study demonstrates that IL-8-Rac1/RhoA-p38MAPK signaling pathway plays a vital role in the IL-8-induced endothelial cell migration, and it provides new insight into the molecular mechanisms by which IL-8 contributes to tumor angiogenesis and metastasis.

Corresponding Author: Liu Xiao-Heng, MD; e-mail: liuxiaohg@scu.edu.cn and liuxiaog@sina.com

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