Leptospira santorosai serovar shermani detergent extract induces an increase in fibronectin production through a toll-like receptor 2-mediated pathway

Ya Chung Tian, Cheng Chieh Hung, Yi Jung Li, Yung Chang Chen, Ming Yang Chang, Tzung Hai Yen, Hsiang Hao Hsu, Mai-Szu Wu, Aled Phillips, Chih Wei Yang

研究成果: 雜誌貢獻文章

14 引文 斯高帕斯(Scopus)

摘要

Leptospirosis can activate inflammatory responses through Toll-like receptors (TLRs) and may cause renal tubulointerstitial fibrosis characterized by the accumulation of extracellular matrix (ECM). We have previously demonstrated that Leptospira santorosai serovar Shermani detergent extract stimulates ECM accumulation in vitro. The aim of this study was to examine the mechanistic basis of these previous observations and, in particular, to examine the potential involvement of TLRs. The addition of serovar Shermani detergent extract led to an increase in fibronectin gene expression and production. Inhibition of TLR2 but not TLR4 expression abrogated serovar Shermani detergent extract-mediated increases in fibronectin production. This response was also blocked by the knockdown of the gene expression of the TLR2 downstream transducers myeloid differentiation factor 88 (MyD88) and tumor necrosis factor receptor-associated factor 6 (TRAF6). Serovar Shermani detergent extract also activated nuclear factor-κB, and its inhibition by curcumin-attenuated serovar Shermani detergent extract induced increases in fibronectin production. These effects were also mimicked by the specific TLR2 agonist, Pam(3)CsK(4), a response that was also abrogated by the knockdown of MyD88 and TRAF6. Similarly, the administration of live leptospires to cells also induced fibronectin production that was blocked by inhibition of TLR2 and MyD88 expression. In conclusion, serovar Shermani detergent extract can induce fibronectin production through the TLR2-associated cascade, providing evidence of an association between TLRs and leptospirosis-mediated ECM deposition.
原文英語
頁(從 - 到)1134-1142
頁數9
期刊Infection and Immunity
79
發行號3
DOIs
出版狀態已發佈 - 三月 2011
對外發佈Yes

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

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    Tian, Y. C., Hung, C. C., Li, Y. J., Chen, Y. C., Chang, M. Y., Yen, T. H., Hsu, H. H., Wu, M-S., Phillips, A., & Yang, C. W. (2011). Leptospira santorosai serovar shermani detergent extract induces an increase in fibronectin production through a toll-like receptor 2-mediated pathway. Infection and Immunity, 79(3), 1134-1142. https://doi.org/10.1128/IAI.01287-09