on September 22, 2005
Published online before print September 22, 2005, doi: 10.1161/01.ATV.0000187468.00675.a3
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Submitted on December 17, 2004
Accepted on September 9, 2005
Toll-Like Receptor 2 Mediates Persistent Chemokine Release by Chlamydia pneumoniae-Infected Vascular Smooth Muscle Cells
Xin Yang ;
From the Molecular Cardiology Research Institute and Department of Medicine (X.Y., D.C, K.S., D.B.), Tufts-New England Medical Center, Boston, and the Division of Infectious Diseases and Immunology (D.T.G.), University of Massachusetts Medical School, Worcester, Mass.
* To whom correspondence should be addressed. E-mail: Dbeasley{at}tufts-nemc.org.
Objective--The intracellular bacterium Chlamydia pneumoniae is present in many atherosclerotic lesions, where it could promote inflammation. This study determined whether monocyte chemoattractant protein 1 (MCP-1) release is stimulated in vascular smooth muscle cells (VSMCs) that are exposed to or infected by C pneumoniae and whether toll-like receptor 2 (TLR2) or TLR4 mediate these effects.
Methods and Results--TLR2 mRNA was expressed constitutively and was upregulated by C pneumoniae exposure in mouse aortic SMC and was inducible by C pneumoniae and TLR3 and TLR4 agonists in human coronary artery SMCs. Exposure to inactivated or viable extracellular C pneumoniae evoked a robust increase in MCP-1 release and activated nuclear factor-
B and extracellular signal-regulated kinase 1/2 in wild-type and TLR4 signaling-deficient mouse aortic SMCs but not in TLR2-deficient SMCs, probably because of TLR2-mediated recognition of a chlamydial antigen. Brief exposure to viable C pneumoniae led to active infection of VSMCs, shown by chlamydial protein synthesis, and caused a persistent (>48-hour) MCP-1 release that was also TLR2 dependent.
Conclusions--The results show that VSMCs express functional TLR2 and that TLR2 mediates both a persistent activation of chemokine release in C pneumoniae-infected VSMCs and its acute stimulation by extracellular C pneumoniae. Therefore, TLR2 expressed in VSMCs may promote inflammation within the arterial wall.
Key words: monocyte chemoattractant protein-1 • nuclear factor-
B •
extracellular signal-regulated kinase 1/2 •
heat shock protein 60 •
lipopolysaccharide
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