PPAR-gamma activation by Tityus serrulatus venom regulates lipid body formation and lipid mediator production

Author(s)

Zoccal, Karina Furlani ^[1] ; Garcia Paula-Silva, Francisco Wanderley ^[1] ; Bitencourt, Claudia da Silva ^[1] ; Sorgi, Carlos Arterio ^[1] ; Figueiredo Bordon, Karla de Castro ^[2] ; Arantes, Eliane Candiani ^[2] ; Faccioli, Lucia Helena ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Anal Clin Toxicol & Bromatol, BR-05508 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Quim & Fis, BR-05508 Sao Paulo - Brazil

• Document type: Journal article
• Source: Toxicon; v. 93, p. 90-97, JAN 2015.
• Web of Science Citations: 15

Abstract

Tityus serrulatus venom (TsV) consists of numerous peptides with different physiological and pharmacological activities. Studies have shown that scorpion venom increases pro-inflammatory cytokine production, contributing to immunological imbalance, multiple organ dysfunction, and patient death. We have previously demonstrated that TsV is a venom-associated molecular pattern (VAMP) recognized by TLRs inducing intense inflammatory reaction through the production of pro-inflammatory cytokines and arachidonic acid-derived lipid mediators prostaglandin (PG)E-2 and leukotriene (LT)B-4. Lipid bodies (LBs) are potential sites for eicosanoid production by inflammatory cells. Moreover, recent studies have shown that the peroxisome proliferator-activated receptor gamma (PPAR-gamma) is implicated in LB formation and acts as an important modulator of lipid metabolism during inflammation. In this study, we used murine macrophages to evaluate whether the LB formation induced by TsV after TLR recognition correlates with lipid mediator generation by macrophages and if it occurs through PPAR-gamma activation. We demonstrate that TsV acts through TLR2 and TLR4 stimulation and PPAR-gamma activation to induce LB formation and generation of PGE(2) and LTB4. Our data also show that PPAR-gamma negatively regulates the pro-inflammatory NF-kappa B transcription factor. Based on these results, we suggest that during envenomation, LBs constitute functional organelles for lipid mediator production through signaling pathways that depend on cell surface and nuclear receptors. These findings point to the inflammatory mechanisms that might also be triggered during human envenomation by TsV. (C) 2014 Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 09/07169-5 - Lipid mediators as regulators of immune response
• Grantee: Lúcia Helena Faccioli
• Support Opportunities: Research Projects - Thematic Grants