IL-4 inhibits cell cycle progression of human umbilical vein endothelial cells by affecting p53, p21Waf1, cyclin D1, and cyclin E expression

초록

IL-4 is emerging as a candidate cytokine for the treatment of inflammatory and autoimmune diseases. We have reported that IL-4 has anti-angiogenic activity and inhibits the growth of human umbilical vein endothelial cells (HUVEC) in response to vascular endothelial growth factor (VEGF) or fibroblast growth factor-2 (FGF-2). Cell cycle analysis of this effect revealed that IL-4 arrests the growth of FGF-2-stimulated HUVEC in G<inf>0</inf> + G<inf>1</inf> phases. The absence of subdiploid cells showed that it did not induce apoptosis. Growth arrest was dose-dependent, but the percentage of G<inf>0</inf> + G<inf>1</inf> phase cells never exceeded 85%. An immunoblot analysis demonstrated that expression of p53 and p21Waf1 was increased and that of cyclin D1 and cyclin E decreased by IL-4. These results show that IL-4 inhibits endothelial cell growth by altering the expression of cell cycle regulatory molecules. ©KSMCB 2003.

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