title: Treponema pallidum flagellins elicit proinflammatory cytokines from human monocytes via TLR5 signaling pathway.
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.affiliation: 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.
authors.forename: Man
authors.initials: M
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Yafeng
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha 410011, China.
authors.forename: Chuanhao
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Department of Clinical Laboratory, The Second Affiliated Hospital of University of South China, Hengyang 421001, China.
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: 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.
authors.forename: Xingxing
authors.initials: X
authors.lastname: Kuang
authors.affiliation: 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.
authors.forename: Yating
authors.initials: Y
authors.lastname: Wen
authors.affiliation: 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.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tan
authors.affiliation: 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.
authors.forename: Manyi
authors.initials: M
authors.lastname: Tan
authors.affiliation: 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.
authors.forename: Feijun
authors.initials: F
authors.lastname: Zhao
authors.affiliation: 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.
authors.forename: Tiebing
authors.initials: T
authors.lastname: Zeng
authors.affiliation: 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.
authors.forename: Yimou
authors.initials: Y
authors.lastname: Wu
mesh_terms: D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004306:Dose-Response Relationship, Immunologic; D005408:Flagellin / Q000276:immunology* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D013587:Syphilis / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051198:Toll-Like Receptor 5 / Q000235:genetics / Q000378:metabolism*; D014210:Treponema pallidum / Q000276:immunology*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D034741:RNA, Small Interfering; D051198:Toll-Like Receptor 5; D005408:Flagellin
keywords: Flagellin; Human monocytes; Inflammation; TLR5 signaling; Treponema pallidum