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C-reactive protein induces VCAM-1 gene expression through NF-kappaB activation in vascular endothelial cells
- Source :
- Atherosclerosis. 185(1)
- Publication Year :
- 2004
-
Abstract
- Recent studies have shown that C-reactive protein (CRP) is not just a predictor of cardiovascular events but also acts directly as a proinflammatory stimulus in vascular cells. In this report, we studied the molecular mechanisms underlying vascular cellular adhesion molecule-1 (VCAM-1) induction by CRP. CRP-induced VCAM-1 mRNA expression and this induction was inhibited by protein kinase C (PKC) inhibitors, p38 mitogen-activated protein kinase (MAPK) inhibitor, and tyrosine kinase inhibitors. In addition, parthenolide, a nuclear factor kappaB (NF-kappaB) inhibitor, abolished VCAM-1 induction. Moreover, CRP increased VCAM-1 promoter activity, indicating that CRP induces VCAM-1 mRNA expression at the transcriptional level. Mutation of NF-kappaB-binding sites resulted in a loss of induction. Finally, an electrophoretic mobility shift assay confirmed binding of the p65 subunit of NF-kappaB to kappaB-binding sites. Taken together, our findings suggest that VCAM-1 induction by CRP is mediated by PKC, p38MAPK, tyrosine kinase and the NF-kappaB-dependent signaling pathways in vascular endothelial cells.
- Subjects :
- MAPK/ERK pathway
Transcriptional Activation
Gene Expression
Vascular Cell Adhesion Molecule-1
In Vitro Techniques
chemistry.chemical_compound
Animals
Humans
RNA, Messenger
VCAM-1
Protein kinase A
Protein kinase C
Aorta
Cells, Cultured
biology
NF-kappa B
Endothelial Cells
Atherosclerosis
Blotting, Northern
FLT4
Molecular biology
C-Reactive Protein
chemistry
Mitogen-activated protein kinase
Mutation
biology.protein
Cattle
Endothelium, Vascular
Signal transduction
Cardiology and Cardiovascular Medicine
Tyrosine kinase
Signal Transduction
Subjects
Details
- ISSN :
- 00219150
- Volume :
- 185
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Atherosclerosis
- Accession number :
- edsair.doi.dedup.....81beea457a8412fabd7218a83041b3d3