title: Treponema pallidum flagellin FlaA2 induces IL-6 secretion in THP-1 cells via the Toll-like receptor 2 signaling pathway.
abstract: Treponema pallidum subsp. pallidum membrane proteins are considered as potent inducers in the initiation and development of inflammation. In the present study, the mechanism that leads to the production of interleukin 6 (IL-6), one of the key proinflammatory cytokines, by human monocytic THP-1 cells when these cells are treated with T. pallidum flagellin FlaA2 was investigated. Stimulation with flagellin FlaA2 can induce IL-6 expression in human monocytes and augment the phosphorylation of ERK, p38, and NF-κB, but has no effect on the phosphorylation of JNK. Likewise, FlaA2-induced IL-6 production was found to be attenuated by inhibitors for ERK, p38, and NF-κB, but not by JNK inhibitor. Immunofluorescence analysis showed that flagellin FlaA2 could stimulate the translocation of IκBα from the cytosol to the nucleus, and this phenomenon could be inhibited by the specific inhibitor BAY11-7082. FlaA2-induced IL-6 expression was also proved to be abrogated by transfection with dominant negative (DN) plasmid of MyD88. We further demonstrated that transfection with DN-TLR2 was sufficient to attenuate IL-6 expression and the phosphorylation of ERK, p38, and IκBα. These results suggest that flagellin FlaA2 induces IL-6 production via signaling pathways involving TLR2, MyD88, ERK, p38, and NF-κB in monocytes, which could contribute to 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; 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: 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: 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; Department of Clinical Laboratory, The Second Affiliated Hospital of University of South China, Hengyang 421001, China.
authors.forename: Zhuoran
authors.initials: Z
authors.lastname: Liu
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: Chuanhao
authors.initials: C
authors.lastname: Jiang
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: Chuan
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, The Second Affiliated Hospital of University of South China, Hengyang 421001, China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Clinical Laboratory, The Second Affiliated Hospital of University of South China, Hengyang 421001, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Clinical Laboratory, The Second Affiliated Hospital of University of South China, Hengyang 421001, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Clinical Laboratory, The Second Affiliated Hospital of University of South China, Hengyang 421001, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, The Second Affiliated Hospital of University of South China, Hengyang 421001, China.
authors.forename: Huaming
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory, The Second Affiliated Hospital of University of South China, Hengyang 421001, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory, The Second Affiliated Hospital of University of South China, Hengyang 421001, China.
authors.forename: Xiaotuan
authors.initials: X
authors.lastname: Zhang
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: Department of Clinical Laboratory, The First Affiliated Hospital of University of South China, Hengyang 421001, China.
authors.forename: Shuangquan
authors.initials: S
authors.lastname: Liu
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: D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005408:Flagellin / Q000276:immunology* / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D051195:Toll-Like Receptor 2 / Q000276:immunology* / Q000378:metabolism; D014210:Treponema pallidum; D014211:Treponemal Infections / Q000276:immunology* / Q000378:metabolism
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D051195:Toll-Like Receptor 2; D005408:Flagellin
keywords: Flagellin FlaA2; Human monocytic cells; IL-6; Inflammation; TLR2 signaling; Treponema pallidum