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 Owain ORCID: https://orcid.org/0000-0001-9744-7113 and Yang, Chih-Wei 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) , pp. 1134-1142. 10.1128/IAI.01287-09

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
Additional Information:	Pdf uploaded in accordance with publisher's policy at http://www.sherpa.ac.uk/romeo/issn/0019-9567/ (accessed 24/02/2014)
Publisher:	American Society for Microbiology
ISSN:	0019-9567
Date of First Compliant Deposit:	30 March 2016
Last Modified:	16 May 2023 04:07
URI:	https://orca.cardiff.ac.uk/id/eprint/27406

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