Recombinant Treponema pallidum protein Tp0136 promotes fibroblast migration by modulating MCP‐1/CCR2 through TLR4

Abstract Background Chancre self‐healing is an important clinical feature in the early stages of syphilis infection. Wound healing may involve an important mechanism by the migration of fibroblasts filling the injured lesion. However, the specific mechanism underlying this process is still unknown. Objectives We aimed to analyse the role of Tp0136 in the migration of fibroblasts and the related mechanism. Methods The migration ability of fibroblasts was detected by a wound‐healing assay. RT ‐ PCR and ELISA detected the expression of MCP ‐1, IL ‐6 and MMP ‐9. TLR 4 expression was detected by RT ‐ PCR . The protein levels of CCR 2 and relevant signalling pathway molecules were measured by Western blotting. Results Tp0136 significantly promoted fibroblast migration. Subsequently, the levels of MCP ‐1 and its receptor CCR 2 were increased in this process. The migration of fibroblasts was significantly inhibited by an anti‐ MCP ‐1 neutralizing antibody or CCR 2 inhibitors. Furthermore, studies demonstrated that Tp0136 could activate the ERK / JNK / PI 3K/ NF ‐κB signalling pathways through TLR 4 activity and that signalling pathways inhibitors could weaken MCP ‐1 secretion and fibroblast migration. Conclusions These findings demonstrate that Tp0136 promotes the migration of fibroblasts by inducing MCP ‐1/ CCR 2 expression through signalling involving the TLR 4, ERK , JNK , PI 3K and NF ‐κB signalling pathways, which could contribute to the mechanism of chancre self‐healing in syphilis.