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

• Published in: Journal of the European Academy of Dermatology and Venereology Vol. 34; no. 4; pp. 862 - 872
• Main Authors: Luo, X., Gao, Z.‐X., Lin, S.‐W., Tong, M.‐L., Liu, L.‐L., Lin, L.‐R., Ke, W.‐J., Yang, T.‐C.
• Format: Journal Article
• Language: English
• Published: England 01-04-2020
• Subjects: Blotting, Western; Cell Movement; Cells, Cultured; Chemokine CCL2 - metabolism; Enzyme-Linked Immunosorbent Assay; Fibroblasts - metabolism; Receptors, CCR2 - metabolism; Recombinant Proteins - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Syphilis - pathology; Toll-Like Receptor 4 - metabolism; Treponema pallidum; Wound Healing - physiology
• ISSN: 0926-9959; 1468-3083
• DOI: 10.1111/jdv.16162

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. TLR4 expression was detected by RT‐PCR. The protein levels of CCR2 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 CCR2 were increased in this process. The migration of fibroblasts was significantly inhibited by an anti‐MCP‐1 neutralizing antibody or CCR2 inhibitors. Furthermore, studies demonstrated that Tp0136 could activate the ERK/JNK/PI3K/NF‐κB signalling pathways through TLR4 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/CCR2 expression through signalling involving the TLR4, ERK, JNK, PI3K and NF‐κB signalling pathways, which could contribute to the mechanism of chancre self‐healing in syphilis.