IL-4 inhibits cell cycle progression of human umbilical vein endothelial cells by affecting p53, p21(Waf1), cyclin D1, and cyclin E expression.
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.
D002453:Cell Cycle / Q000502:physiology*; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000378:metabolism*; D019927:Cyclin E / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
C493956:CDKN1A protein, human; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D019938:Cyclin D1; D015847:Interleukin-4