C-reactive protein activates the nuclear
factor-kappaB pathway and induces
vascular cell adhesion molecule-1
expression through CD32 in human
umbilical vein endothelial cells and aortic
endothelial cells
徐國基
Liang YJ;Shyu KG;Wang BW;Lai LP
摘要
Abstract
C-reactive protein (CRP) contributes to the process of atherosclerosis by inducing pro-inflammatory changes in endothelial cells. However, the exact receptor involved in CRP-induced endothelial changes remains unclear. Human umbilical vein endothelial cells (HUVECs) and human aortic
endothelial cells (HAECs) were used for the experiments. After incubation with CRP, immunoblotting showed a significant decrease of IKB protein and
electrophoretic mobility shift assay showed a significant increase of nuclear NF-KB binding capacity. These changes were associated with a significant increase of vascular cell adhesion molecule-1 (VCAM-1) expression. The mRNA level of CD32, the major binding protein for CRP in endothelial cells, increased significantly as measured by Northern blot and Western blot. When these cells were transfected with siRNA directed against CD32, the mRNA of CD32 decreased significantly. The IKB degradation, NF-KB nuclear
translocation and VCAM-1 up-regulation induced by CRP were all inhibited by treatment with siRNA against CD32. SB203580, a P38 inhibitor, significantly attenuated the CRP-induced responses while SP600125 (c-jun kinase inhibitor) did not. In conclusion, CRP-induced IκB degradation, NF-KB nuclear
translocation and VCAM-1 protein expression in HUVECs and HAECs. CRP also increased the expression of CD32, which might serve as the receptor for
