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Evaluation of intracellular mechanism of the immunomodulatory effect of epoxyeicosatrienoic acids and the inhibition of soluble Epoxide Hydrolase in a arthritis model

Grant number: 19/21176-6
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): December 18, 2019
Effective date (End): December 17, 2020
Field of knowledge:Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
Principal Investigator:Juliana Trindade Clemente Napimoga
Grantee:Carlos Antonio Trindade da Silva
Supervisor abroad: Bruce D. Hammock
Home Institution: Centro de Pesquisas Odontológicas São Leopoldo Mandic. Faculdade São Leopoldo Mandic (SLMANDIC). Sociedade Regional de Ensino e Saúde S/S Ltda (SRES). Campinas , SP, Brazil
Research place: University of California, Davis (UC Davis), United States  
Associated to the scholarship:19/01151-9 - Evaluation of the immunomodulatory and neuroprotective effect of the epoxy hydrolase inhibitor, TPPU, on persistent inflammatory hypernociception induced by arthritis in the temporomandibular joint of rats., BP.PD

Abstract

Epoxyeicosatrienoic acids (EETs) are products of arachidonic acid metabolism catalyzed by cytochrome P450 epoxygenases. These small molecules are autocrine and paracrine lipid mediators with important roles in inflammation, cardiovascular function, and angiogenesis. Recent evidence has highlighted that EETs could represent a novel therapeutic strategy for the control of inflammation. The presence of EETs in tissues and their metabolism by soluble epoxide hydrolase (sEH) to 1,2-diols were first reported 30 years ago. However, appreciation of their importance in cell biology and physiology has greatly accelerated over the past decade with the discovery of metabolically stable inhibitors of sEH, such as TPPU (1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)), the commercial availability of EETs, and the development of analytical methods for the quantification of EETs and their diols. Rheumatoid arthritis (RA) is a chronic inflammatory disorder that affect millions of people. The current available treatments, disease-modifying anti-rheumatic drugs (DMARDs), has shown some side effects like severe immunosuppression and opportunistic infections. Thus, new therapeutic targets are needed to treat RA. The pharmacological approach presented here is different from the available drugs since the inhibitor used increase the activity of an endogenous anti-inflammatory pathway. The present study aimed to investigate whether sEH inhibitor (TPPU) and EETs may modulate polalization of lyphocytes in a arthritis model and see the effects on osteoclast cells to elucidate the involved molecular mechanisms.