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

Autor(es)

Moreira, Vanessa ; Teixeira, Catarina ; da Silva, Henrique Borges ; D'Imperio Lima, Maria Regina ; Dos-Santos, Maria Cristina

• Tipo de documento: Artigo Científico
• Fonte: Toxicon; v. 118, p. 121-128, AUG 2016.
• Citações Web of Science: 5

Resumo

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-1 beta, IL-6 and LTB4; protein expression of COX-1 and COX-2; and quantification of their products PGE(2) and TXA(2). 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-1 beta and LTB4 and reduced mononuclear leukocyte influx. However, no significant differences in COX 2 protein expression or PGE(2), TXA(2) 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. (C) 2016 Elsevier Ltd. All rights reserved. (AU)

• Processo FAPESP: 11/21341-5 - Estudo de mecanismos envolvidos na formação de corpúsculos lipídicos induzidos por uma fosfolipase A2 isolada do veneno da serpente Bothrops asper em macrófagos isolados: participação de fatores da homeostasia lipídica
• Beneficiário: Catarina de Fatima Pereira Teixeira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/00810-5 - Priming por IFN-gama durante a fase crônica da malária experimental: estudo dos mecanismos moleculares e efetores envolvidos
• Beneficiário: Henrique Borges da Silva
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/07140-2 - Papel dos inflamassomas na patogenia da tuberculose causada por isolados clínicos hipervirulentos de micobactérias
• Beneficiário: Maria Regina D'Império Lima
• Modalidade de apoio: Auxílio à Pesquisa - Regular