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Proinflammatory phenotype of vascular smooth muscle cells: role of efficient Toll-like receptor 4 signaling.
- Source :
-
American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2005 Sep; Vol. 289 (3), pp. H1069-76. Date of Electronic Publication: 2005 Apr 29. - Publication Year :
- 2005
-
Abstract
- Recent evidence supports a role of Toll-like receptor (TLR) signaling in the development of atherosclerotic lesions. In this study, we tested whether TLR4 signaling promotes a proinflammatory phenotype in human and mouse arterial smooth muscle cells (SMC), characterized by increased cytokine and chemokine synthesis and increased TLR expression. Human arterial SMC were found to express mRNA encoding TLR4 and the TLR4-associated molecules MD-2 and CD14 but not TLR2 mRNA. Mouse aortic SMC, on the other hand, expressed both TLR2 and TLR4 mRNA constitutively. Human SMC derived from the coronary artery, but not those from the pulmonary artery, were found to express cell surface-associated CD14. Low concentrations (ng/ml) of Escherichia coli LPS, the prototypical TLR4 agonist, markedly stimulated extracellular regulated kinase 1/2 (ERK1/2) activity, induced release of monocyte-chemoattractant protein-1 (MCP-1) and interleukin (IL)-6, and stimulated IL-1alpha expression in human aortic SMC, and exogenous CD14 enhanced these effects. Expression of a dominant negative form of TLR4 in human SMC attenuated LPS-induced ERK1/2 and MCP-1 release. LPS was a potent inducer of NF-kappaB activity, ERK1/2 phosphorylation, MCP-1 release, and TLR2 mRNA expression in wild-type mice but not in TLR4-signaling deficient mouse aortic SMC. These studies show that TLR4 signaling promotes a proinflammatory phenotype in vascular smooth muscle cells (VSMC) and suggest that VSMC may potentially play an active role in vascular inflammation via the release of chemokines, proinflammatory cytokines, and increased expression of TLR2.
- Subjects :
- Animals
Antigens, Surface genetics
Aorta cytology
Carrier Proteins genetics
Cells, Cultured
Chemokine CCL2 metabolism
Humans
Interleukin-1 biosynthesis
Interleukin-6 metabolism
Lipopolysaccharide Receptors genetics
Lipopolysaccharide Receptors pharmacology
Lipopolysaccharides pharmacology
Lymphocyte Antigen 96
Mice
Mitogen-Activated Protein Kinase 1 metabolism
Mitogen-Activated Protein Kinase 3 metabolism
Muscle, Smooth, Vascular cytology
Muscle, Smooth, Vascular drug effects
NF-kappa B metabolism
Phenotype
RNA, Messenger analysis
Toll-Like Receptor 2
Toll-Like Receptor 4
Toll-Like Receptors
Vasculitis immunology
Membrane Glycoproteins genetics
Muscle, Smooth, Vascular physiology
Receptors, Cell Surface genetics
Signal Transduction immunology
Vasculitis physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 0363-6135
- Volume :
- 289
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Heart and circulatory physiology
- Publication Type :
- Academic Journal
- Accession number :
- 15863460
- Full Text :
- https://doi.org/10.1152/ajpheart.00143.2005