Inflammatory effect of Bothropstoxin-I from the Bothrops jararacussu venom mediated by NLRP3 inflammasome involves ATP and P2X7 receptor
Clin Sci (Lond), v. 135, n. 5, p. 687-701, fev. 2021
Article
em En
| SES-SP, SESSP-IBPROD, SES-SP
| ID: bud-3584
Biblioteca responsável:
BR78.1
ABSTRACT
Muscle tissue damage is one of the local effects described in bothropic envenomations. Bothropstoxin-I (BthTX-I), from B. jararacussu venom, is a K49-phospholipase A2 that induces a massive muscle tissue injury, and, consequently, local inflammatory reaction. The NLRP3 inflammasome is a sensor that triggers inflammation by activating caspase 1 and releasing IL-1b and/or inducing pyroptotic cell death in response to tissue damage. We, therefore, aimed to address activation of NLRP3 inflammasome by BthTX-I-associated injury and the mechanism involved in this process. Intramuscular injection of BthTX-I results in infiltration of neutrophils and macrophages in gastrocnemius muscle, which is reduced in NLRP3- and Caspase-1-deficient mice. The in vitro IL-1β production induced by BthTX-I- inperitoneal macrophages requires caspase 1/11, ASC and NLRP3 and is dependent of ATP-induced K+ efflux and P2X7R. BthTX-I induces a dramatic release of ATP from C2C12 myotubes, therefore representing the major mechanism for P2X7R-dependent inflammasome activation in macrophages. A similar result was obtained when human monocyte-derived macrophages were treated with BthTX-I. These findings demonstrated the inflammatory effect of BthTX-I on muscle tissue, pointing out a role for the ATP released by damaged cells for the NLRP3 activation on macrophages, contributing to the understanding of the microenvironment of the tissue damage of the Bothrops envenomation.
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1
Coleção SES:
Producao_cientifica
Base de dados:
SES-SP
/
SESSP-IBPROD
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article