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

Autor(es)

Moreira, Vanessa ^[1] ; Teixeira, Catarina ^[1] ; da Silva, Henrique Borges ^[2] ; D'Imperio Lima, Maria Regina ^[2] ; Dos-Santos, Maria Cristina ^[3]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Toxicon; v. 67, p. 37-46, JUN 1 2013.
• Citações Web of Science: 10

Resumo

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)

• Processo FAPESP: 10/51150-4 - Modelo animal para análise da patogenicidade de cepas de Mycobacterium bovis e avaliação da resposta imune celular e humoral contra isolados patogênicos
• Beneficiário: Maria Regina D'Império Lima
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 07/03336-9 - Estudo de efeitos de duas fosfolipases A2, isoladas do veneno de serpente, sobre vias de ativação do NF-kB relacionados à expressão de COX-2 e de PGE sintase M-1: envolvimento do receptor de manose
• Beneficiário: Catarina de Fatima Pereira Teixeira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 09/08559-1 - Caracterização dos mecanismos efetores da imunidade inata e adquirida no modelo de malária crônica em camundongos CD28KO infectados pelo Plasmodium chabaudi AS
• Beneficiário: Henrique Borges da Silva
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 07/03337-5 - Efeito de duas fosfolipases A2, isoladas do veneno de serpente, sobre vias de ativação do NF-kapa b relacionadas à expressão de COX-2 e de PGE sintase m-1: envolvimento do receptor de manose de macrófagos nesses eventos
• Beneficiário: Vanessa Moreira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado