Study of the role of PLIN2 in inflammatory response induced by MT-III, a Phospholipase A2 isolated from Bothrops asper snake venom: lipid bodies biogenesis and release of inflammatory mediators

Abstract

Bothrops venoms contain high concentrations of secreted phospholipases A2 (sPLA2) which have structural and functional homology with mammalian PLA2s, whose levels are increased in inflammatory diseases such as atherosclerosis. We have recently demonstrated that MT-III, a sPLA2 group IIA, induced an increase in lipid body formation and expression of adipofilina (ADRP) or PLIN2, a protein involved in lipid metabolism and related to the accumulation of lipids in lipid bodies. However, the role of PLIN2 in the inflammatory response induced by MT-III has not been elucidated. Thus, this study aims to evaluate the effects of MT-III in macrophages depleted for PLIN2, with emphasis on factors involved in triggering the inflammatory response. The aim of this study is to assess the role of PLIN2 in the inflammatory effects induced by the snake venom sPLA2 MT-III in depleted macrophages to PLIN2, such as: 1) lipid body formation, 2) release of the lipid mediators (PGE2, PGD2, LTB4) and proinflammatory cytokines (TNF-alfa, IL-1B and IL-6) 3) arachidonic acid incorporation into triacylglycerol. This work will contribute to understanding the role of PLIN2 the inflammatory response induced by MT-III, a secreted phospholipases A2, and intracellular processes that regulate the accumulation of lipids in immunocompetent cells, in addition to better understanding of the pathophysiology of local reaction caused by Bothrops venoms. Still, this work may show new therapeutic targets in diseases in which the inflammatory response and lipid imbalance are triggers factors. (AU)