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.
Pharmacology Laboratory, Butantan Institute, São Paulo, SP, Brazil.
Vanessa
V
Moreira
Pharmacology Laboratory, Butantan Institute, São Paulo, SP, Brazil.
Catarina
C
Teixeira
Immunology Department, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Henrique
H
Borges da Silva
Immunology Department, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Maria Regina
MR
D'Império Lima
Immunochemistry Laboratory, Parasitology Department, Institute of Biological Sciences, Federal University of Amazonas, Manaus, AM, Brazil. Electronic address: mcsantos@ufam.edu.br.
Maria Cristina
MC
Dos-Santos
D000818:Animals; D017837:Bothrops; D001938:Brazil; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005122:Exudates and Transudates / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018836:Inflammation Mediators / Q000097:blood; D007958:Leukocyte Count; D007962:Leukocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction / Q000187:drug effects*; D012909:Snake Bites / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D013047:Specific Pathogen-Free Organisms; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D014757:Viper Venoms / Q000633:toxicity*
D016207:Cytokines; D018836:Inflammation Mediators; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D014757:Viper Venoms
Bothrops atrox snake venom; Cytokines; Eicosanoids; Mediators of inflammation; TLR2