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Recombinant Treponema pallidum protein Tp47 promotes the migration and adherence of THP-1 cells to human dermal vascular smooth muscle cells by inducing MCP-1 and ICAM-1 expression.
Exp Cell Res 2019; 381(1):150-162EC

Abstract

Vascular inflammation is a complex and multifactorial pathophysiological process that plays a crucial role in all stages of syphilis and is responsible for tissue damage. Little is known about the interactions of infiltrating immunocytes with human dermal vascular smooth muscle cells (HDVSMCs) in arterioles during the immunopathogenesis of syphilis. The Treponema pallidum subsp. pallidum membrane protein Tp47 is considered a major inducer of inflammation initiation and development. In this study, we demonstrated that Tp47 promoted the migration and adhesion of THP-1 cells to HDVSMCs. Furthermore, Tp47 increased monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule-1 (ICAM-1) mRNA and protein expression levels in a dose- and time-dependent manner. The migration and adhesion of THP-1 cells to HDVSMCs were significantly suppressed by anti-MCP-1 and anti-ICAM-1 neutralizing antibodies, respectively. Further studies revealed that treatment of HDVSMCs with Tp47 activated the PI3K/Akt, p38 MAPK and NF-κB signalling pathways. Inhibition of PI3K/Akt, p38 MAPK and NF-κB suppressed the MCP-1 and ICAM-1 expression induced by Tp47. In addition, the migration and adhesion of THP-1 cells to Tp47-treated HDVSMCs were significantly decreased by pretreatment with PI3K/Akt, p38 MAPK and NF-κB inhibitors. These findings demonstrate that Tp47 promotes the migration and adherence of THP-1 cells to HDVSMCs by inducing MCP-1 and ICAM-1 expression, which is mediated by activation of the PI3K/Akt, p38 MAPK and NF-κB pathways. This study provides a novel potential therapeutic strategy for controlling the vascular inflammatory response in syphilis patients.

Authors+Show Affiliations

Center of Clinical Laboratory, Zhongshan Hospital, School of Medicine, Xiamen University, Xiamen, 361004, China; Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, 361004, China.Center of Clinical Laboratory, Zhongshan Hospital, School of Medicine, Xiamen University, Xiamen, 361004, China.Center of Clinical Laboratory, Zhongshan Hospital, School of Medicine, Xiamen University, Xiamen, 361004, China; Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, 361004, China.Center of Clinical Laboratory, Zhongshan Hospital, School of Medicine, Xiamen University, Xiamen, 361004, China; Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, 361004, China.Center of Clinical Laboratory, Zhongshan Hospital, School of Medicine, Xiamen University, Xiamen, 361004, China.Center of Clinical Laboratory, Zhongshan Hospital, School of Medicine, Xiamen University, Xiamen, 361004, China; Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, 361004, China. Electronic address: niujianjun211@xmu.edu.cn.Center of Clinical Laboratory, Zhongshan Hospital, School of Medicine, Xiamen University, Xiamen, 361004, China; Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, 361004, China. Electronic address: yangtianci@xmu.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31075255

Citation

Gao, Zheng-Xiang, et al. "Recombinant Treponema Pallidum Protein Tp47 Promotes the Migration and Adherence of THP-1 Cells to Human Dermal Vascular Smooth Muscle Cells By Inducing MCP-1 and ICAM-1 Expression." Experimental Cell Research, vol. 381, no. 1, 2019, pp. 150-162.
Gao ZX, Liu D, Liu LL, et al. Recombinant Treponema pallidum protein Tp47 promotes the migration and adherence of THP-1 cells to human dermal vascular smooth muscle cells by inducing MCP-1 and ICAM-1 expression. Exp Cell Res. 2019;381(1):150-162.
Gao, Z. X., Liu, D., Liu, L. L., Lin, L. R., Tong, M. L., Niu, J. J., & Yang, T. C. (2019). Recombinant Treponema pallidum protein Tp47 promotes the migration and adherence of THP-1 cells to human dermal vascular smooth muscle cells by inducing MCP-1 and ICAM-1 expression. Experimental Cell Research, 381(1), pp. 150-162. doi:10.1016/j.yexcr.2019.04.035.
Gao ZX, et al. Recombinant Treponema Pallidum Protein Tp47 Promotes the Migration and Adherence of THP-1 Cells to Human Dermal Vascular Smooth Muscle Cells By Inducing MCP-1 and ICAM-1 Expression. Exp Cell Res. 2019 Aug 1;381(1):150-162. PubMed PMID: 31075255.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Recombinant Treponema pallidum protein Tp47 promotes the migration and adherence of THP-1 cells to human dermal vascular smooth muscle cells by inducing MCP-1 and ICAM-1 expression. AU - Gao,Zheng-Xiang, AU - Liu,Dan, AU - Liu,Li-Li, AU - Lin,Li-Rong, AU - Tong,Man-Li, AU - Niu,Jian-Jun, AU - Yang,Tian-Ci, Y1 - 2019/05/07/ PY - 2019/01/27/received PY - 2019/04/25/revised PY - 2019/04/29/accepted PY - 2019/5/11/pubmed PY - 2019/5/11/medline PY - 2019/5/11/entrez KW - Chemoattractant protein-1 KW - Human dermal vascular smooth muscle cells KW - Intercellular adhesion molecule-1 KW - THP-1 cells KW - Treponema pallidum SP - 150 EP - 162 JF - Experimental cell research JO - Exp. Cell Res. VL - 381 IS - 1 N2 - Vascular inflammation is a complex and multifactorial pathophysiological process that plays a crucial role in all stages of syphilis and is responsible for tissue damage. Little is known about the interactions of infiltrating immunocytes with human dermal vascular smooth muscle cells (HDVSMCs) in arterioles during the immunopathogenesis of syphilis. The Treponema pallidum subsp. pallidum membrane protein Tp47 is considered a major inducer of inflammation initiation and development. In this study, we demonstrated that Tp47 promoted the migration and adhesion of THP-1 cells to HDVSMCs. Furthermore, Tp47 increased monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule-1 (ICAM-1) mRNA and protein expression levels in a dose- and time-dependent manner. The migration and adhesion of THP-1 cells to HDVSMCs were significantly suppressed by anti-MCP-1 and anti-ICAM-1 neutralizing antibodies, respectively. Further studies revealed that treatment of HDVSMCs with Tp47 activated the PI3K/Akt, p38 MAPK and NF-κB signalling pathways. Inhibition of PI3K/Akt, p38 MAPK and NF-κB suppressed the MCP-1 and ICAM-1 expression induced by Tp47. In addition, the migration and adhesion of THP-1 cells to Tp47-treated HDVSMCs were significantly decreased by pretreatment with PI3K/Akt, p38 MAPK and NF-κB inhibitors. These findings demonstrate that Tp47 promotes the migration and adherence of THP-1 cells to HDVSMCs by inducing MCP-1 and ICAM-1 expression, which is mediated by activation of the PI3K/Akt, p38 MAPK and NF-κB pathways. This study provides a novel potential therapeutic strategy for controlling the vascular inflammatory response in syphilis patients. SN - 1090-2422 UR - https://www.unboundmedicine.com/medline/citation/31075255/Recombinant_Treponema_pallidum_protein_Tp47_promotes_the_migration_and_adherence_of_THP_1_cells_to_human_dermal_vascular_smooth_muscle_cells_by_inducing_MCP_1_and_ICAM_1_expression_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4827(19)30226-5 DB - PRIME DP - Unbound Medicine ER -