IL-4 inhibits cell cycle progression of human umbilical vein endothelial cells by affecting p53, p21(Waf1), cyclin D1, and cyclin E expression

• Published in: Molecules and cells Vol. 16; no. 1; p. 92
• Main Authors: Kim, Jinkoo, Cheon, In Su, Won, Yu-Jin, Na, Hee Jun, Kim, Young-Myeong, Choe, Jongseon
• Format: Journal Article
• Language: English
• Published: United States 31-08-2003
• Subjects: Cell Cycle - physiology; Cells, Cultured; Cyclin D1 - metabolism; Cyclin E - metabolism; Cyclin-Dependent Kinase Inhibitor p21; Cyclins - metabolism; Endothelial Cells - cytology; Endothelial Cells - metabolism; Fibroblast Growth Factor 2 - metabolism; Humans; Interleukin-4 - metabolism; Tumor Suppressor Protein p53 - metabolism; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 1016-8478

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 G0 + G1 phases. The absence of subdiploid cells showed that it did not induce apoptosis. Growth arrest was dose-dependent, but the percentage of G0 + G1 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.