Effect of C-reactive protein on chemokine expression in human aortic endothelial cells.
Inflammation plays a pivotal role in atherosclerosis. In addition to being a risk marker for cardiovascular disease, much recent data support a role for C-reactive protein (CRP) in atherogenesis. Interleukin-8 (IL-8), a member of the CXC chemokines promotes monocyte-endothelial cell adhesion and arrest and is abundant in atherosclerotic plaques. However, there is a paucity of data examining the effect of CRP on IL-8 secretion in human aortic endothelial cells (HAEC). In this report, we show that incubation of HAEC with CRP resulted in a time and dose-dependent increase in IL-8 protein and mRNA via transcription. In contrast to human umbilical vein endothelial cells, monocyte-chemoattractant protein-1 expression in HAEC was not affected by CRP. Furthermore, CRP upregulated NF-kappa B activity in HAEC and inhibitors of NF-kappa B significantly reversed the upregulation of IL-8 by CRP. Blocking antibodies to IL-8 significantly decreased monocyte-endothelial cell adhesion induced by CRP (31%, P<0.01). In conclusion, this study makes the novel observation that CRP induces IL-8 synthesis and secretion in HAEC via upregulation of NF-kappa B activity.
Devaraj
Sridevi
S
Laboratory for Atherosclerosis and Metabolic Research, Department of Pathology, University of California, Davis Medical Center, 4635 Second Avenue, Research 1 Building, Rm 3000, Sacramento, CA 95817, USA.
Kumaresan
Pappanaicken R
PR
Jialal
Ishwarlal
I
D001011:Aorta / Q000166:cytology*; D001161:Arteriosclerosis / Q000378:metabolism; D002097:C-Reactive Protein / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012717:Sesquiterpenes / Q000494:pharmacology
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016209:Interleukin-8; D016328:NF-kappa B; D010455:Peptides; D012333:RNA, Messenger; C118258:SN50 peptide; D012717:Sesquiterpenes; C002669:parthenolide; D002097:C-Reactive Protein