Chlamydia pneumoniae Infection Promotes Vascular Smooth Muscle Cell Migration through a Toll-Like Receptor 2-Related Signaling Pathway
ABSTRACTThe migration of vascular smooth muscle cells (VSMCs) from the media to the intima is proposed to be a key event in the development of atherosclerosis. Recently, we reported thatChlamydia pneumoniaeinfection is involved in VSMC migration. However, the exact mechanisms forC. pneumoniaeinfection-induced VSMC migration are not yet well elucidated. In this study, we examined the role of the Toll-like receptor 2 (TLR2) activation-related signaling pathway in VSMC migration induced byC. pneumoniaeinfection. An Affymetrix-based gene expression array was conducted to identify the changes of gene expression in rat primary VSMCs (rVSMCs) infected withC. pneumoniae. Both the microarray analysis and quantitative real-time reverse transcription (RT)-PCR revealed that TLR2 mRNA expression was strongly upregulated 12 h afterC. pneumoniaeinfection. RT-PCR and Western blot analysis further showed that the expression levels of TLR2 mRNA and protein significantly increased at the different time points after infection. Immunocytochemical analysis suggested a TLR2 recruitment to the vicinity ofC. pneumoniaeinclusions. Cell migration assays showed that the TLR2-neutralizing antibody could significantly inhibitC. pneumoniaeinfection-induced rVSMC migration. In addition,C. pneumoniaeinfection stimulated Akt phosphorylation at Ser 473, which was obviously suppressed by the PI3K inhibitor LY294002, thereby inhibiting rVSMC migration caused byC. pneumoniaeinfection. Furthermore, both the infection-induced Akt phosphorylation and rVSMC migration were suppressed by the TLR2-neutralizing antibody. Taken together, these data suggest thatC. pneumoniaeinfection can promote VSMC migration possibly through the TLR2-related signaling pathway.