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Akt, mTOR and NF-κB pathway activation in Treponema pallidum stimulates M1 macrophages.
Int Immunopharmacol 2018; 59:181-186II

Abstract

The polarization of macrophages and the molecular mechanism involved during the early process of syphilis infection remain unknown. This study was conducted to explore the influence of Treponema pallidum (T. pallidum) treatment on macrophage polarization and the Akt-mTOR-NFκB signaling pathway mechanism involved in this process. M0 macrophages derived from the phorbol-12-myristate-13-acetate-induced human acute monocytic leukemia cell line THP-1 were cultured with T. pallidum. T. pallidum induced inflammatory cytokine (IL-1β and TNF-α) expression in a dose- and time-dependent manner. However IL-10 cytokine expression decreased at the mRNA and protein levels. Additionally, the expression of the M1 surface marker iNOS was up-regulated with incubation time, and the expression of the M2 surface marker CD206 was low (vs. PBS treated macrophages, P < 0.001) and did not fluctuate over 12 h. Further studies revealed that Akt-mTOR-NFκB pathway proteins, including p-Akt, p-mTOR, p-S6, p-p65, and p-IκBα, were significantly higher in the T. pallidum-treated macrophages than in the PBS-treated macrophages (P < 0.05). In addition, inflammatory cytokine expression was suppressed in T. pallidum-induced M1 macrophages pretreated with LY294002 (an Akt-specific inhibitor) or PDTC (an NF-κB inhibitor), while inflammatory cytokine levels increased in T. pallidum-induced M1 macrophages pretreated with rapamycin (an mTOR inhibitor). These findings revealed that T. pallidum promotes the macrophage transition to pro-inflammatory M1 macrophages in vitro. The present study also provides evidence that Akt, mTOR and NF-κB pathway activation in T. pallidum stimulates M1 macrophages. This study provides novel insights into the innate immune response to T. pallidum infection.

Authors+Show Affiliations

Zhongshan Hospital, Medical College of Xiamen University, Xiamen 361004, China; Institute of Infectious Disease, Medical College of Xiamen University, Xiamen 361004, China.Zhongshan Hospital, Medical College of Xiamen University, Xiamen 361004, China.Zhongshan Hospital, Medical College of Xiamen University, Xiamen 361004, China; Institute of Infectious Disease, Medical College of Xiamen University, Xiamen 361004, China.Zhongshan Hospital, Medical College of Xiamen University, Xiamen 361004, China; Institute of Infectious Disease, Medical College of Xiamen University, Xiamen 361004, China.Zhongshan Hospital, Medical College of Xiamen University, Xiamen 361004, China.Zhongshan Hospital, Medical College of Xiamen University, Xiamen 361004, China.Zhongshan Hospital, Medical College of Xiamen University, Xiamen 361004, China.Zhongshan Hospital, Medical College of Xiamen University, Xiamen 361004, China; Institute of Infectious Disease, Medical College of Xiamen University, Xiamen 361004, China.Zhongshan Hospital, Medical College of Xiamen University, Xiamen 361004, China; Institute of Infectious Disease, Medical College of Xiamen University, Xiamen 361004, China.Zhongshan Hospital, Medical College of Xiamen University, Xiamen 361004, China; Institute of Infectious Disease, Medical College of Xiamen University, Xiamen 361004, China.Zhongshan Hospital, Medical College of Xiamen University, Xiamen 361004, China; Institute of Infectious Disease, Medical College of Xiamen University, Xiamen 361004, China.Zhongshan Hospital, Medical College of Xiamen University, Xiamen 361004, China; Institute of Infectious Disease, Medical College of Xiamen University, Xiamen 361004, China. Electronic address: niujianjun@xmu.edu.cn.Institute of Infectious Disease, Medical College of Xiamen University, Xiamen 361004, China; Medical College of Xiamen University, Xiamen 361004, China. Electronic address: liufan@xmu.edu.cn.Zhongshan Hospital, Medical College of Xiamen University, Xiamen 361004, China; Institute of Infectious Disease, Medical College of Xiamen University, Xiamen 361004, China. Electronic address: yangtianci@xmu.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29656208

Citation

Lin, Li-Rong, et al. "Akt, mTOR and NF-κB Pathway Activation in Treponema Pallidum Stimulates M1 Macrophages." International Immunopharmacology, vol. 59, 2018, pp. 181-186.
Lin LR, Gao ZX, Lin Y, et al. Akt, mTOR and NF-κB pathway activation in Treponema pallidum stimulates M1 macrophages. Int Immunopharmacol. 2018;59:181-186.
Lin, L. R., Gao, Z. X., Lin, Y., Zhu, X. Z., Liu, W., Liu, D., ... Yang, T. C. (2018). Akt, mTOR and NF-κB pathway activation in Treponema pallidum stimulates M1 macrophages. International Immunopharmacology, 59, pp. 181-186. doi:10.1016/j.intimp.2018.03.040.
Lin LR, et al. Akt, mTOR and NF-κB Pathway Activation in Treponema Pallidum Stimulates M1 Macrophages. Int Immunopharmacol. 2018;59:181-186. PubMed PMID: 29656208.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Akt, mTOR and NF-κB pathway activation in Treponema pallidum stimulates M1 macrophages. AU - Lin,Li-Rong, AU - Gao,Zheng-Xiang, AU - Lin,Yong, AU - Zhu,Xiao-Zhen, AU - Liu,Wei, AU - Liu,Dan, AU - Gao,Kun, AU - Tong,Man-Li, AU - Zhang,Hui-Lin, AU - Liu,Li-Li, AU - Xiao,Yao, AU - Niu,Jian-Jun, AU - Liu,Fan, AU - Yang,Tian-Ci, Y1 - 2018/04/12/ PY - 2018/01/31/received PY - 2018/03/20/revised PY - 2018/03/30/accepted PY - 2018/4/16/pubmed PY - 2018/10/9/medline PY - 2018/4/16/entrez KW - AKT KW - Macrophage KW - Polarization KW - Treponema pallidum KW - mTOR SP - 181 EP - 186 JF - International immunopharmacology JO - Int. Immunopharmacol. VL - 59 N2 - The polarization of macrophages and the molecular mechanism involved during the early process of syphilis infection remain unknown. This study was conducted to explore the influence of Treponema pallidum (T. pallidum) treatment on macrophage polarization and the Akt-mTOR-NFκB signaling pathway mechanism involved in this process. M0 macrophages derived from the phorbol-12-myristate-13-acetate-induced human acute monocytic leukemia cell line THP-1 were cultured with T. pallidum. T. pallidum induced inflammatory cytokine (IL-1β and TNF-α) expression in a dose- and time-dependent manner. However IL-10 cytokine expression decreased at the mRNA and protein levels. Additionally, the expression of the M1 surface marker iNOS was up-regulated with incubation time, and the expression of the M2 surface marker CD206 was low (vs. PBS treated macrophages, P < 0.001) and did not fluctuate over 12 h. Further studies revealed that Akt-mTOR-NFκB pathway proteins, including p-Akt, p-mTOR, p-S6, p-p65, and p-IκBα, were significantly higher in the T. pallidum-treated macrophages than in the PBS-treated macrophages (P < 0.05). In addition, inflammatory cytokine expression was suppressed in T. pallidum-induced M1 macrophages pretreated with LY294002 (an Akt-specific inhibitor) or PDTC (an NF-κB inhibitor), while inflammatory cytokine levels increased in T. pallidum-induced M1 macrophages pretreated with rapamycin (an mTOR inhibitor). These findings revealed that T. pallidum promotes the macrophage transition to pro-inflammatory M1 macrophages in vitro. The present study also provides evidence that Akt, mTOR and NF-κB pathway activation in T. pallidum stimulates M1 macrophages. This study provides novel insights into the innate immune response to T. pallidum infection. SN - 1878-1705 UR - https://www.unboundmedicine.com/medline/citation/29656208/Akt_mTOR_and_NF_κB_pathway_activation_in_Treponema_pallidum_stimulates_M1_macrophages_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1567-5769(18)30143-7 DB - PRIME DP - Unbound Medicine ER -