Banca de DEFESA: YODA JANAINA IKENOHUCHI

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : YODA JANAINA IKENOHUCHI
DATE: 01/06/2023
TIME: 07:30
LOCAL: Sala Virtual Remora
TITLE:

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KEY WORDS:

Venom lectin. BjcuL. PBMCs. Inflammasome NLRP3.

PAGES: 74
BIG AREA: Ciências Biológicas
AREA: Biologia Geral
SUMMARY:

Lectins are a large group of proteins found in all snake venoms. BjcuL, a C-type lectin, isolated from Bothrops jararacussu snake venom, does not have a cytotoxic effect on human peripheral blood mononuclear cells (PBMCs), but demonstrates an immunomodulatory role, inducing the production of pro- and anti-inflammatory cytokines (IL -2, IL-10, IFN-γ, IL-6, TNF-α, and IL-17), in addition to stimulating T cells to produce reactive oxygen species (ROS), which may play a role in the observed acute inflammatory reaction in victims of envenoming. ROS production can trigger the activation of the NLRP3 inflammasome complex. Inflammasomes are essential in innate immunity cells, detect various endogenous or exogenous, sterile or infectious stimuli, and stimulate cellular responses and effector mechanisms. The NLRP3 inflammasome is an important target, as the lectin is responsible for the activation of leukocytes that stimulates the release of inflammatory mediators resulting in dynamic cellular responses to restore homeostasis in snakebite victims. Thus, this study aimed to investigate the action of BjcuL isolated from Bothrops jararacussu snake venom on activating the NLRP3 inflammasome complex in human PBMCs. PBMCs were isolated by density gradient and incubated with BjcuL at different periods and concentrations. Activation of the inflammasome complex was evaluated through gene and protein expression of ASC, CASPASE-1, and NLRP3 by RTq-PCR, Western blot, and immunofluorescence, as well as the participation of Toll-like receptor 4 (TLR4) and mitochondrial ROS (mROS) in the production of IL-1β, a product resulting from the activation of the NLRP3 inflammasome. The data showed that BjcuL interacts with TLR4 and induces cytokine release via NF-κB signaling. It was demonstrated by gene and protein expression assays, that BjcuL activates the NLRP3 inflammasome, and pharmacological modulation with LPS-RS, TLR4 antagonist; LPS-SM, TLR4 agonist; MCC950, a specific NLRP3 inhibitor; and rotenone, an mROS inhibitor, confirmed the activation of the inflammasome through the release of its product IL-1β, and also the participation of TLR4 and mROS. It was verified that the effects of BjcuL in the regulation and activation of the NLRP3 inflammasome complex via activation of TLR4 with the participation of mROS can be a determinant for the development of the local inflammatory effects observed in victims of envenoming.

COMMITTEE MEMBERS:
Externo à Instituição - FABIO HENRIQUE KWASNIEWSKI - UEL
Presidente - 1726461 - JULIANA PAVAN ZULIANI TRENCH DE SOUZA
Interno - ***.335.462-** - SORAYA DOS SANTOS PEREIRA - UNIR