Toll-like receptor 2 mediates persistent chemokine release by Chlamydia pneumoniae-infected vascular smooth muscle cells.
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.


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-kappaB 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.
Yang
Xin
X
Molecular Cardiology Research Institute, Department of Medicine, Tufts-New England Medical Center, Boston, MA, USA.
Coriolan
Daniel
D
Schultz
Kelly
K
Golenbock
Douglas T
DT
Beasley
Debbie
D
D000818:Animals; D001011:Aorta / Q000166:cytology; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism*; D002690:Chlamydia Infections / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D016993:Chlamydophila pneumoniae; D003331:Coronary Vessels / Q000166:cytology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000382:microbiology* / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014657:Vasculitis / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*
D018925:Chemokines; D012333:RNA, Messenger; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4