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Tityus serrulatus scorpion venom is recognized by pattern recognition receptors and induces cell activation and inflammation

Grant number: 10/18179-9
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): February 01, 2011
Effective date (End): August 31, 2014
Field of knowledge:Biological Sciences - Immunology - Applied Immunology
Principal researcher:Lúcia Helena Faccioli
Grantee:Karina Furlani Zoccal
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:09/07169-5 - Lipid mediators as regulators of immune response, AP.TEM

Abstract

Tityus serrulatus is the scorpion considered one of the most dangerous species to humans in Brazil, which venom induces local and systemic inflammatory response. In this project, we aimed to study in this project, we aimed to study the inflammatory mediators production, cell activation and receptors of innate immunity responsible for recognition of the venom of the scorpion T. serrulatus (TsV) as well as their toxins. We have demonstrated that TsV and their toxins Ts1 and Ts6 induce NO, IL-6 and TNF-± production in J774.1 cells, which may be potentiated by presence of LPS. However, Ts2 exhibits anti-inflammatory activity due induction of IL-10 production and inhibits the release of NO, IL- 6 and TNF-± induced by LPS. We also show that Ts2 or Ts6 isolated of TsV, besides of the cytokines, induce the production of lipid mediators (LTB4 and PGE2), and these mediators contribute to leukocytes recruitment into the peritoneal cavity. Taken together, our data demonstrated that Ts2 and Ts6 induce inflammation by mechanisms dependent on the production of cytokines and lipid mediators, and that Ts2 may play regulatory role on the cell response. Furthermore, continuing our studies, we demonstrated that TLR2, TLR4 and CD14 receptors recognize TsV, mediating cytokines and lipid mediators production. We also showed TsV MyD88-dependent activation of NF-ºB, and a MyD88-independent activation of the factor c-Jun. Similar to TsV, the majority toxin Ts1 induces MyD88-dependent phosphorylation of NF-kB via TLR2 and TLR4 recognition, while the c-Jun activation is through TLR4 recognition, but independent of MyD88. Within this context, we propose the term Venom-Associated Molecular Pattern (VAMP), to refer molecules that are introduced into the host by stings and recognized by PRRs, resulting in inflammation. Finally, we investigated the formation of lipid bodies (LBs) and generation of eicosanoids, through TsV recognition by TLR2 and TLR4. Our data showed that eicosanoid production correlates with the LBs formation, which are dependent on TLR2, TLR4 and PPAR³ activation, suggesting that this nuclear receptor can modulate cytokines inflammatory. Thus, we suggest that PPAR³ may be an attractive candidate target for novel therapeutic strategies to prevent the deleterious effects of intense systemic release of inflammatory mediators after envenomation. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ZOCCAL, KARINA FURLANI; BITENCOURT, CLAUDIA DA SILVA; GARCIA PAULA-SILVA, FRANCISCO WANDERLEY; SORGI, CARLOS ARTERIO; FIGUEIREDO BORDON, KARLA DE CASTRO; ARANTES, ELIANE CANDIANI; FACCIOLI, LUCIA HELENA. TLR2, TLR4 and CD14 Recognize Venom-Associated Molecular Patterns from Tityus serrulatus to Induce Macrophage-Derived Inflammatory Mediators. PLoS One, v. 9, n. 2 FEB 7 2014. Web of Science Citations: 31.

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