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Treponema pallidum flagellins elicit proinflammatory cytokines from human monocytes via TLR5 signaling pathway.
Immunobiology 2017; 222(5):709-718I

Abstract

The tissue damage caused by syphilis infection may be associated with inflammation. However, the virulence factors of Treponema pallidum are still unclear, nor are the molecular mechanisms for leading to the productions of proinflammatory cytokines. Flagellin, a classic pathogen-associated molecular pattern (PAMP), is a potent immunogen that induces inflammation. In the present study, we have demonstrated that stimulations of human monocytes with Treponema pallidum FlaB1, FlaB2, and FlaB3 result in the up regulation of interleukin (IL)-6 and IL-8. Moreover, silencing of the Toll-like receptor 5 (TLR5) gene by using small interfering RNA was found to abrogate the T. pallidum flagellins-induced IL-6 and IL-8 expressions. Similarly, transfection with the dominant negative plasmid encoding MyD88 (pDeNy-hMyD88) was also giving rise to the down regulation of IL-6 and IL-8. We further investigated the relative contributions of mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) signaling to transcriptions and translations of IL-6 and IL-8. Western Blot and immuno fluorescence experiments revealed that flagellins-mediated IL-6 and IL-8 expressions are heavily dependent on ERK, p38, and NF-κB. In addition, inhibitions of p38 kinase, ERK, and NF-κB were found to attenuate the productions of IL-6 and IL-8. Taken together, our results indicate that T. pallidum flagellins can upregulate IL-6 and IL-8 generations via TLR5 and MAPK/NF-κB signaling pathways in THP-1 cells, which will improve our understanding of the pathogenesis of T. pallidum.

Authors+Show Affiliations

Institution of Pathogenic Biology, Medical College, University of South China; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China; Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang 421001, China.Institution of Pathogenic Biology, Medical College, University of South China; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China; Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang 421001, China; Department of Clinical Laboratory, The Second Affiliated Hospital of University of South China, Hengyang 421001, China.Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha 410011, China.Department of Clinical Laboratory, The Second Affiliated Hospital of University of South China, Hengyang 421001, China.Institution of Pathogenic Biology, Medical College, University of South China; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China; Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang 421001, China.Institution of Pathogenic Biology, Medical College, University of South China; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China; Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang 421001, China.Institution of Pathogenic Biology, Medical College, University of South China; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China; Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang 421001, China.Institution of Pathogenic Biology, Medical College, University of South China; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China; Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang 421001, China.Institution of Pathogenic Biology, Medical College, University of South China; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China; Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang 421001, China.Institution of Pathogenic Biology, Medical College, University of South China; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China; Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang 421001, China.Institution of Pathogenic Biology, Medical College, University of South China; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China; Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang 421001, China. Electronic address: yimouwu@sina.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28126263

Citation

Xu, Man, et al. "Treponema Pallidum Flagellins Elicit Proinflammatory Cytokines From Human Monocytes Via TLR5 Signaling Pathway." Immunobiology, vol. 222, no. 5, 2017, pp. 709-718.
Xu M, Xie Y, Jiang C, et al. Treponema pallidum flagellins elicit proinflammatory cytokines from human monocytes via TLR5 signaling pathway. Immunobiology. 2017;222(5):709-718.
Xu, M., Xie, Y., Jiang, C., Xiao, Y., Kuang, X., Wen, Y., ... Wu, Y. (2017). Treponema pallidum flagellins elicit proinflammatory cytokines from human monocytes via TLR5 signaling pathway. Immunobiology, 222(5), pp. 709-718. doi:10.1016/j.imbio.2017.01.002.
Xu M, et al. Treponema Pallidum Flagellins Elicit Proinflammatory Cytokines From Human Monocytes Via TLR5 Signaling Pathway. Immunobiology. 2017;222(5):709-718. PubMed PMID: 28126263.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Treponema pallidum flagellins elicit proinflammatory cytokines from human monocytes via TLR5 signaling pathway. AU - Xu,Man, AU - Xie,Yafeng, AU - Jiang,Chuanhao, AU - Xiao,Yongjian, AU - Kuang,Xingxing, AU - Wen,Yating, AU - Tan,Yuan, AU - Tan,Manyi, AU - Zhao,Feijun, AU - Zeng,Tiebing, AU - Wu,Yimou, Y1 - 2017/01/21/ PY - 2016/12/17/received PY - 2017/01/14/revised PY - 2017/01/14/accepted PY - 2017/1/28/pubmed PY - 2017/12/8/medline PY - 2017/1/28/entrez KW - Flagellin KW - Human monocytes KW - Inflammation KW - TLR5 signaling KW - Treponema pallidum SP - 709 EP - 718 JF - Immunobiology JO - Immunobiology VL - 222 IS - 5 N2 - The tissue damage caused by syphilis infection may be associated with inflammation. However, the virulence factors of Treponema pallidum are still unclear, nor are the molecular mechanisms for leading to the productions of proinflammatory cytokines. Flagellin, a classic pathogen-associated molecular pattern (PAMP), is a potent immunogen that induces inflammation. In the present study, we have demonstrated that stimulations of human monocytes with Treponema pallidum FlaB1, FlaB2, and FlaB3 result in the up regulation of interleukin (IL)-6 and IL-8. Moreover, silencing of the Toll-like receptor 5 (TLR5) gene by using small interfering RNA was found to abrogate the T. pallidum flagellins-induced IL-6 and IL-8 expressions. Similarly, transfection with the dominant negative plasmid encoding MyD88 (pDeNy-hMyD88) was also giving rise to the down regulation of IL-6 and IL-8. We further investigated the relative contributions of mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) signaling to transcriptions and translations of IL-6 and IL-8. Western Blot and immuno fluorescence experiments revealed that flagellins-mediated IL-6 and IL-8 expressions are heavily dependent on ERK, p38, and NF-κB. In addition, inhibitions of p38 kinase, ERK, and NF-κB were found to attenuate the productions of IL-6 and IL-8. Taken together, our results indicate that T. pallidum flagellins can upregulate IL-6 and IL-8 generations via TLR5 and MAPK/NF-κB signaling pathways in THP-1 cells, which will improve our understanding of the pathogenesis of T. pallidum. SN - 1878-3279 UR - https://www.unboundmedicine.com/medline/citation/28126263/Treponema_pallidum_flagellins_elicit_proinflammatory_cytokines_from_human_monocytes_via_TLR5_signaling_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0171-2985(17)30002-5 DB - PRIME DP - Unbound Medicine ER -