PMID- 31075255 OWN - NLM STAT- MEDLINE DCOM- 20200615 LR - 20200615 IS - 1090-2422 (Electronic) IS - 0014-4827 (Linking) VI - 381 IP - 1 DP - 2019 Aug 1 TI - 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. PG - 150-162 LID - S0014-4827(19)30226-5 [pii] LID - 10.1016/j.yexcr.2019.04.035 [doi] AB - 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-kappaB signalling pathways. Inhibition of PI3K/Akt, p38 MAPK and NF-kappaB 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-kappaB 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-kappaB pathways. This study provides a novel potential therapeutic strategy for controlling the vascular inflammatory response in syphilis patients. CI - Copyright (c) 2019. Published by Elsevier Inc. FAU - Gao, Zheng-Xiang AU - Gao ZX AD - 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. FAU - Liu, Dan AU - Liu D AD - Center of Clinical Laboratory, Zhongshan Hospital, School of Medicine, Xiamen University, Xiamen, 361004, China. FAU - Liu, Li-Li AU - Liu LL AD - 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. FAU - Lin, Li-Rong AU - Lin LR AD - 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. FAU - Tong, Man-Li AU - Tong ML AD - Center of Clinical Laboratory, Zhongshan Hospital, School of Medicine, Xiamen University, Xiamen, 361004, China. FAU - Niu, Jian-Jun AU - Niu JJ AD - 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. FAU - Yang, Tian-Ci AU - Yang TC AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190507 PL - United States TA - Exp Cell Res JT - Experimental cell research JID - 0373226 RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (ICAM1 protein, human) RN - 0 (NF-kappa B) RN - 0 (Recombinant Proteins) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - EC 3.5.2.6 (Tp47 protein, Treponema pallidum) RN - EC 3.5.2.6 (beta-Lactamases) SB - IM MH - Cell Adhesion MH - Cell Movement MH - Cells, Cultured MH - Chemokine CCL2/metabolism MH - Dermis/metabolism/pathology MH - Humans MH - Intercellular Adhesion Molecule-1/metabolism MH - Muscle, Smooth, Vascular/*metabolism/pathology MH - NF-kappa B/metabolism MH - Phosphorylation MH - Proto-Oncogene Proteins c-akt/metabolism MH - Recombinant Proteins MH - Signal Transduction MH - Syphilis/metabolism/*microbiology/pathology MH - THP-1 Cells MH - Treponema pallidum/*physiology MH - beta-Lactamases/genetics/*physiology MH - p38 Mitogen-Activated Protein Kinases/metabolism OTO - NOTNLM OT - Chemoattractant protein-1 OT - Human dermal vascular smooth muscle cells OT - Intercellular adhesion molecule-1 OT - THP-1 cells OT - Treponema pallidum EDAT- 2019/05/11 06:00 MHDA- 2020/06/17 06:00 CRDT- 2019/05/11 06:00 PHST- 2019/01/27 00:00 [received] PHST- 2019/04/25 00:00 [revised] PHST- 2019/04/29 00:00 [accepted] PHST- 2019/05/11 06:00 [pubmed] PHST- 2020/06/17 06:00 [medline] PHST- 2019/05/11 06:00 [entrez] AID - S0014-4827(19)30226-5 [pii] AID - 10.1016/j.yexcr.2019.04.035 [doi] PST - ppublish SO - Exp Cell Res. 2019 Aug 1;381(1):150-162. doi: 10.1016/j.yexcr.2019.04.035. Epub 2019 May 7.