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

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1134-1142
Number of pages9
JournalInfection and Immunity
Volume79
Issue number3
DOIs
Publication statusPublished - Mar 2011
Externally publishedYes

Fingerprint

Toll-Like Receptor 2
Leptospira
Fibronectins
Detergents
Myeloid Differentiation Factor 88
Toll-Like Receptors
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
Extracellular Matrix
Leptospirosis
Gene Expression
Curcumin
Transducers
Serogroup
Fibrosis
Kidney

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Leptospira santorosai serovar shermani detergent extract induces an increase in fibronectin production through a toll-like receptor 2-mediated pathway. / Tian, Ya Chung; Hung, Cheng Chieh; Li, Yi Jung; Chen, Yung Chang; Chang, Ming Yang; Yen, Tzung Hai; Hsu, Hsiang Hao; Wu, Mai-Szu; Phillips, Aled; Yang, Chih Wei.

In: Infection and Immunity, Vol. 79, No. 3, 03.2011, p. 1134-1142.

Research output: Contribution to journalArticle

Tian, Ya Chung ; Hung, Cheng Chieh ; Li, Yi Jung ; Chen, Yung Chang ; Chang, Ming Yang ; Yen, Tzung Hai ; Hsu, Hsiang Hao ; Wu, Mai-Szu ; Phillips, Aled ; Yang, Chih Wei. / Leptospira santorosai serovar shermani detergent extract induces an increase in fibronectin production through a toll-like receptor 2-mediated pathway. In: Infection and Immunity. 2011 ; Vol. 79, No. 3. pp. 1134-1142.
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AU - Chen, Yung Chang

AU - Chang, Ming Yang

AU - Yen, Tzung Hai

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