IL-4 Inhibits Cell Cycle Progression of Human Umbilical Vein Endothelial Cells by Affecting p53, p21~(Waf1), Cyclin D1, and Cyclin E Expression

摘要

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_0 + G_1 phases. The absence of subdiploid cells showed that it did not induce apoptosis. Growth arrest was dose-dependent, but the percentage of G_0 + G_1 phase cells never exceeded 85%. An immunoblot analysis demonstrated that expression of p53 and p21~(Waf1) 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.