The role of TLR2 in the acute inflammatory response induced by Bothrops atrox snake venom

Vanessa Moreira; Catarina Teixeira; Henrique Borges Da Silva; Maria Regina D'Império Lima; Maria Cristina Dos-Santos

doi:10.1016/j.toxicon.2016.04.042

The role of TLR2 in the acute inflammatory response induced by Bothrops atrox snake venom

Vanessa Moreira, Catarina Teixeira, Henrique Borges Da Silva, Maria Regina D'Império Lima, Maria Cristina Dos-Santos

Laboratory Medicine and Pathology

Research output: Contribution to journal › Article › peer-review

27 Scopus citations

Abstract

Envenomation by snakes of the species Bothrops atrox induces local and systemic effects. Local effects include drastic tissue damage and a marked inflammatory response as a result of the synthesis and release of a variety of protein and lipid mediators. Toll-like receptor (TLR) signaling pathways can play an important role in this response, leading to synthesis of these inflammatory mediators. This study investigated the influence of TLR2 on the acute inflammatory response induced by Bothrops atrox venom. Wild-type C57BL/6 mice (WT) and TLR2 gene knockout mice (TLR2^-/-) were injected with Bothrops atrox venom (BaV), and the following responses to the venom were assessed in peritoneal exudate: leukocyte accumulation; release of mediators, including CCL-2, IL-10, IL-1β, IL-6 and LTB₄; protein expression of COX-1 and COX-2; and quantification of their products PGE₂ and TXA₂. After injection with BaV, the TLR2^-/- mice (TLR2^-/-_BaV) had higher levels of IL-6 and CCL-2 than WT animals kept under the same conditions (WT_BaV), together with an accumulation of polymorphonuclear leukocytes (PMNs), inhibition of IL-1β and LTB₄ and reduced mononuclear leukocyte influx. However, no significant differences in COX-2 protein expression or PGE₂, TXA₂ and IL-10 production between the TLR2^-/-_BaV and WT_Bav animals were observed. Together, these results indicate that the signaling pathway activated by TLR2 acts by modulating the induced inflammatory response to BaV through the direct action of venom-associated molecular patterns (VAMPs) or indirectly by forming damage-associated molecular patterns (DAMPs) and that this may have important therapeutic implications.

Original language	English (US)
Pages (from-to)	121-128
Number of pages	8
Journal	Toxicon
Volume	118
DOIs	https://doi.org/10.1016/j.toxicon.2016.04.042
State	Published - Aug 1 2016

Bibliographical note

Funding Information:
The authors would like to thank Renata Hage Amaral for providing technical assistance and Professor Antônio Luiz Ribeiro Boechat Lopes for helping with the statistical analysis. This investigation was supported by research grants from FAPESP , Brazil (ref. no. 2011/21341-5 ). CT is the recipient of a CNPq-PQ grant (ref. no. 306920/2011-5 ); VM is the recipient of a postdoctoral fellowship from Capes-Brazil; MCS is the recipient of a CNPq-PQ grant (ref. no. 303786/2013-2 ); HBS is the recipient of a postdoctoral fellowship from FAPESP (ref. no. 2014/00810-5 ); and MRDL is the recipient of CNPq-PQ (ref. nos. 303676/2014-0 and 448765/2014-4 ) and FAPESP grants (ref. no. 2013/07140-2 ).

Keywords

Bothrops atrox snake venom
Cytokines
Eicosanoids
Mediators of inflammation
TLR2

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title = "The role of TLR2 in the acute inflammatory response induced by Bothrops atrox snake venom",

abstract = "Envenomation by snakes of the species Bothrops atrox induces local and systemic effects. Local effects include drastic tissue damage and a marked inflammatory response as a result of the synthesis and release of a variety of protein and lipid mediators. Toll-like receptor (TLR) signaling pathways can play an important role in this response, leading to synthesis of these inflammatory mediators. This study investigated the influence of TLR2 on the acute inflammatory response induced by Bothrops atrox venom. Wild-type C57BL/6 mice (WT) and TLR2 gene knockout mice (TLR2-/-) were injected with Bothrops atrox venom (BaV), and the following responses to the venom were assessed in peritoneal exudate: leukocyte accumulation; release of mediators, including CCL-2, IL-10, IL-1β, IL-6 and LTB4; protein expression of COX-1 and COX-2; and quantification of their products PGE2 and TXA2. After injection with BaV, the TLR2-/- mice (TLR2-/-BaV) had higher levels of IL-6 and CCL-2 than WT animals kept under the same conditions (WTBaV), together with an accumulation of polymorphonuclear leukocytes (PMNs), inhibition of IL-1β and LTB4 and reduced mononuclear leukocyte influx. However, no significant differences in COX-2 protein expression or PGE2, TXA2 and IL-10 production between the TLR2-/-BaV and WTBav animals were observed. Together, these results indicate that the signaling pathway activated by TLR2 acts by modulating the induced inflammatory response to BaV through the direct action of venom-associated molecular patterns (VAMPs) or indirectly by forming damage-associated molecular patterns (DAMPs) and that this may have important therapeutic implications.",

keywords = "Bothrops atrox snake venom, Cytokines, Eicosanoids, Mediators of inflammation, TLR2",

author = "Vanessa Moreira and Catarina Teixeira and {Borges Da Silva}, Henrique and {D'Imp{\'e}rio Lima}, {Maria Regina} and Dos-Santos, {Maria Cristina}",

note = "Funding Information: The authors would like to thank Renata Hage Amaral for providing technical assistance and Professor Ant{\^o}nio Luiz Ribeiro Boechat Lopes for helping with the statistical analysis. This investigation was supported by research grants from FAPESP , Brazil (ref. no. 2011/21341-5 ). CT is the recipient of a CNPq-PQ grant (ref. no. 306920/2011-5 ); VM is the recipient of a postdoctoral fellowship from Capes-Brazil; MCS is the recipient of a CNPq-PQ grant (ref. no. 303786/2013-2 ); HBS is the recipient of a postdoctoral fellowship from FAPESP (ref. no. 2014/00810-5 ); and MRDL is the recipient of CNPq-PQ (ref. nos. 303676/2014-0 and 448765/2014-4 ) and FAPESP grants (ref. no. 2013/07140-2 ).",

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AU - Dos-Santos, Maria Cristina

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The role of TLR2 in the acute inflammatory response induced by Bothrops atrox snake venom

Abstract

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Keywords

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