ABSTRACT
The role of interleukin-4 (IL-4) in the inflammatory process has emerged recently. In this study, we investigated the effect of IL-4 on the angiogenic process in an in vitro experimental system. IL-4 significantly inhibited the proliferation of human umbilical vein endothelial cells (HUVEC) that was induced by the vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). VEGF- or bFGF-induced HUVEC chemotaxis was abrogated by the IL-4 treatment. In addition, the formation of tube-like structures by HUVEC in the presence of VEGF or bFGF was also severely down-regulated by IL-4. The inhibitory effects on the critical steps of angiogenesis were not observed with IL-6 that is abundantly found in the inflamed tissue. Our results suggest that IL-4 may play a regulatory role in normal physiology and provide the potential possibility for IL-4 as a therapeutic agent in the intervention of angiogenesis-related diseases.
Subject(s)
Endothelial Growth Factors/pharmacology , Fibroblast Growth Factor 2/pharmacology , Intercellular Signaling Peptides and Proteins/pharmacology , Interleukin-4/pharmacology , Lymphokines/pharmacology , Neovascularization, Physiologic/drug effects , Chemotaxis/drug effects , Down-Regulation , Drug Antagonism , Humans , In Vitro Techniques , Neovascularization, Physiologic/physiology , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth FactorsABSTRACT
PURPOSE: Oxidative stress has been implicated in the pathogenesis of various diseases. Catalase is one of the main defense mechanisms against oxidative stress. To examine the possible relationship between oxidative stress, and gastric and hepatocellular carcinomas, HinfI restriction length polymorphism (RFLP) in the human catalase gene was assessed. MATERIALS AND METHODS: The genotype and allele frequencies in the promoter region of the catalase gene were studied by PCR-RFLP in 108 Korean controls, 80 Korean gastric carcinoma (GC) and 106 Korean hepatocellular carcinoma (HCC) patients. RESULTS: No statistically significant differences were found in the genotypic distribution and allelic frequencies between the controls and both types of carcinoma patient. CONCLUSION: To address the possible contribution of oxidative stresses to the pathogenesis of gastric and hepatocellular carcinomas, the associations between the catalase gene polymorphism and GC and HCC susceptibilities were studied. As a result, the catalase gene polymorphism was found not to be determinant of GC and HCC susceptibilities. Further studies are required on various other oxidative stress related genes to elucidate the mechanisms of GC and HCC.
