Inflammasome NLRP3 activation induced by Convulxin, a C-type lectin-like isolated from Crotalus durissus terrificus snake venom

Abstract

Convulxin (CVX), a C-type lectin-like protein isolated from the venom of the snake species, Crotalus durissus terrificus, stimulates platelet aggregation by acting as a collagen receptor agonist for glycoprotein VI found in the platelets. The effect of CVX on platelets has been studied, but its effect on human peripheral blood mononuclear cells (PBMCs) remains unclear. Given the significance of PBMCs in inflammation, this study explored the effect of CVX on PBMCs, specifically regarding NLRP3 inflammasome activation by assessing cell viability, ability to induce cell proliferation, reactive oxygen species (ROS) and nitric oxide production, interleukin (IL)-2 and IL-10 secretion, NLRP3 complex activation, and the role of C-type lectin-like receptors (CTLRs) in these. CVX was not toxic to PBMCs at the investigated concentrations and did not increase PBMC growth or IL-2 release; however, CVX induced IL-10 release and ROS generation via monocyte activation. It also activated the NLRP3 complex, resulting in IL-1β induction. Furthermore, the interaction between CVX and Dectin-2, a CTLR, induced IL-10 production. CVX interaction with CTLR has been demonstrated by laminarin therapy. Because of the involvement of residues near the Dectin-2 carbohydrate-recognition site, the generation of ROS resulted in inflammasome activation and IL-1β secretion. Overall, this work helps elucidate the function of CVX in immune system cells.

Phytochemical Profile, Antioxidant Potential and Toxicity Evaluation of the Essential Oils from Duguetia and Xylopia Species (Annonaceae) from the Brazilian Amazon

“…Molecular modeling approaches have been used to investigate how natural compounds interact with molecular targets of pharmacological interest [ 75 , 76 , 77 , 78 ]. One of the tools used has been molecular docking, which can provide insights into how these compounds interact with the binding pocket of proteins.…”

Studies on the Phytochemical Profile of Ocimum basilicum var. minimum (L.) Alef. Essential Oil, Its Larvicidal Activity and In Silico Interaction with Acetylcholinesterase against Aedes aegypti (Diptera: Culicidae)

“…Molecular modeling approaches have been successfully used to evaluate the interaction of major volatile compounds with molecular targets of pharmacological interest [ 45 , 46 , 47 ]. We used AChE as a molecular target because this enzyme is a promising molecular target for essential oils with larvicidal activity [ 9 ].…”

Molecular Modeling Approaches Can Reveal the Molecular Interactions Established between a Biofilm and the Bioactive Compounds of the Essential Oil of Piper divaricatum

“…In this paper, we utilize molecular modeling approaches to fill the gap related to the molecular investigation of the structure of gelatin biofilms impregnated with bioactive compounds. This methodology has been used to investigate molecular systems of different types [25][26][27][28][29]. As a basis for our studies, we used the structure proposed by Hanani et al (2014) [30] to build the gelatin, and the work of Albuquerque et al (2020) [31] inspired us to carry out our molecular investigations.…”