Treponema pallidum flagellins stimulate MMP-9 and MMP-13 expression via TLR5 and MAPK/NF-κB signaling pathways in human epidermal keratinocytes
| Autor: | Yimou Wu, Yafeng Xie, Jinhong Xiao, Manyi Tan, Chuanhao Jiang, Yongjian Xiao, Feijun Zhao, Man Xu, Xingxing Kuang |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Keratinocytes Biology Microbiology 03 medical and health sciences 0302 clinical medicine Matrix Metalloproteinase 13 Humans Treponema pallidum Cells Cultured Mitogen-Activated Protein Kinase 1 Innate immune system Treponema Pathogen-associated molecular pattern NF-kappa B Cell Biology biology.organism_classification Cell biology TLR2 HaCaT Toll-Like Receptor 5 030104 developmental biology Matrix Metalloproteinase 9 TLR5 030220 oncology & carcinogenesis Signal transduction Flagellin Signal Transduction |
| Zdroj: | Experimental cell research. 361(1) |
| ISSN: | 1090-2422 |
| Popis: | Syphilis is a chronic disease caused by Treponema pallidum and the pathogenesis is still unclear. T. pallidum infection induced inflammatory responses are involved in the immunopathological damage in skin and other tissues. Flagellin, the monomeric subunit of bacterial flagella, is a classic pathogen associated molecular patterns (PAMPs) that interacts to TLR5 and induces inflammatory responses. Keratinocytes, as immune sentinels recognize the PAMPs via TLRs, play an important role in skin innate immune response. Matrix metalloproteinases (MMPs) expressed by keratinocytes are involved in skin inflammatory responses and promoting pathogens invasion. In this study, we demonstrate that FlaB1, FlaB2 and FlaB3, the flagellins of T. pallidum, induced MMP-9 and MMP-13 production in human immortalized keratinocytes cell line HaCaT. Silencing of TLR5, but not TLR2 and TLR4 attenuated MMP-9 and MMP-13 expressions induced by T. pallidum flagellins. MMP-9 and MMP-13 expressions were also be abrogated by transfection with a dominant negative (DN) plasmid of MyD88. We also found that treatment of HaCaT cells with FlaB1, FlaB2 and FlaB3 activate the MAPK and NF-κB signaling pathways. Inhibited of ERK, JNK, p38 and NF-κB suppressed MMP-9 expression induced by the FlaB1. MMP-13 expression was found to be suppressed by pretreatment with inhibitors of ERK, JNK and NF-κB, but not p38. These findings demonstrate that T. pallidum flagellins (FlaB1, FlaB2 or FlaB3) can stimulate MMP-9 and MMP-13 expression through TLR5 and MAPK/NF-κB signaling pathways in human epidermal keratinocytes, which could contribute to the pathogenesis of T. pallidum infection. |
| Databáze: | OpenAIRE |
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