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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:2308.)
© 2005 American Heart Association, Inc.

Vascular Biology

Toll-Like Receptor 2 Mediates Persistent Chemokine Release by Chlamydia pneumoniae–Infected Vascular Smooth Muscle Cells

Xin Yang; Daniel Coriolan; Kelly Schultz; Douglas T. Golenbock; Debbie Beasley

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.

Correspondence to Debbie Beasley, PhD, New England Medical Center, Box 8486, 750 Washington St, Boston, MA, 02111. 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.

TLR2 is expressed constitutively in mouse VSMCs, its expression is inducible in human VSMCs, and it mediates both persistent stimulation of MCP-1 release in SMCs infected with C pneumoniae and acute stimulation by extracellular C pneumoniae. Activation of 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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