The role of TLR2 in the acute inflammatory response induced by Bothrops atrox snake venom.
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.
['Moreira|Vanessa|V|', 'Teixeira|Catarina|C|', 'Borges da Silva|Henrique|H|', "D'Império Lima|Maria Regina|MR|", 'Dos-Santos|Maria Cristina|MC|']
D000818:Animals D017837:Bothrops D001938:Brazil D016207:Cytokines D004195:Disease Models, Animal D005122:Exudates and Transudates D018836:Inflammation Mediators D007958:Leukocyte Count D007962:Leukocytes D008297:Male D008810:Mice, Inbred C57BL D018345:Mice, Knockout D015398:Signal Transduction D012909:Snake Bites D013047:Specific Pathogen-Free Organisms D051195:Toll-Like Receptor 2 D014757:Viper Venoms
TLR2 Bothrops atrox snake venom Cytokines Eicosanoids Mediators of inflammation