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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

The crucial role of the MyD88 adaptor protein in the inflammatory response induced by Bothrops atrox venom

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Author(s):
Moreira, Vanessa [1] ; Teixeira, Catarina [1] ; da Silva, Henrique Borges [2] ; D'Imperio Lima, Maria Regina [2] ; Dos-Santos, Maria Cristina [3]
Total Authors: 5
Affiliation:
[1] Inst Butantan, Farmacol Lab, Sao Paulo - Brazil
[2] Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, BR-05508 Sao Paulo - Brazil
[3] Univ Fed Amazonas, Inst Ciencias Biol, Dept Parasitol, Lab Imunol, BR-69077000 Manaus, AM - Brazil
Total Affiliations: 3
Document type: Journal article
Source: Toxicon; v. 67, p. 37-46, JUN 1 2013.
Web of Science Citations: 10
Abstract

Most snake accidents in North Brazil are attributed to Bothrops atrox, a snake species of the Viperidae family whose venom simultaneously induces local and systemic effects in the victims. The former are clinically more important than the latter, as they cause severe tissue lesions associated with strong inflammatory responses. Although several studies have shown that inflammatory mediators are produced in response to B. atrox venom (Bay), there is little information concerning the molecular pathways involved in innate immune system signaling. Myeloid differentiation factor 88 (MyD88) is an adaptor molecule responsible for transmitting intracellular signals from most toll-like receptors (TLRs) after they interact with pathogen-associated molecular patterns (PAMPs) or other stimuli such as endogenous damage-associated molecular patterns (DAMPs). The MyD88-dependent pathway leads to activation of transcription factors, which in turn induce synthesis of inflammatory mediators such as eicosanoids, cytokines and chemokines. The aim of this study was to investigate the involvement of MyD88 on the acute inflammatory response induced by BaV. Wild-type (WT) C57BL/6 mice and MyD88 knockout (MyD88(-/-)) mice were intraperitoneally injected with BaV. Compared to WT mice, MyD88(-/-) animals showed an impaired inflammatory response to BaV, with lower influx of polymorphonuclear and mononuclear cells to the peritoneal cavity. Furthermore, peritoneal leukocytes from Bay-injected MyD88(-/-) mice did not induce COX-2 or LTB4 protein expression and released low concentrations of PGE(2). These mice also failed to produce Th1 and Th17 cytokines and CCL-2, but IL-10 levels were similar to those of BaV-injected WT mice. Our results indicate that MyD88 signaling is required for activation of the inflammatory response elicited by BaV, raising the possibility of developing new therapeutic targets to treat Bothrops sp. poisoning. (C) 2013 Elsevier Ltd. All rights reserved. (AU)

FAPESP's process: 10/51150-4 - Animal model for analysis of the pathogenicity of Mycobacterium bovis strains and evaluation of cellular and humoral immune responses against pathogenic isolates
Grantee:Maria Regina D'Império Lima
Support Opportunities: Regular Research Grants
FAPESP's process: 09/08559-1 - Characterization of effector mechanisms of innate and acquired immunity in chronic malaria model of CD28KO mice infected with Plasmodium chabaudi AS
Grantee:Henrique Borges da Silva
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 07/03337-5 - Effects of two phospholipases A2, isolated from snake venom on NF-kappaB activation pathways related to COX-2 and mPGE synthase-1 expression: involvement of macrophage mannose receptors
Grantee:Vanessa Moreira
Support Opportunities: Scholarships in Brazil - Post-Doctoral