Title: Soluble epoxide hydrolase inhibitor, TPPU, increases regulatory T cells pathway in an arthritis model.
Authors: Trindade-da-Silva, Carlos A; Clemente-Napimoga, Juliana T; Abdalla, Henrique B; Rosa, Sergio Marcolino; Ueira-Vieira, Carlos; Morisseau, Christophe; Verri Jr, Waldiceu A; Montalli, Victor Angelo Martins; Hammock, Bruce D; Napimoga, Marcelo H
Published In FASEB J, (2020 07)
Abstract: Epoxyeicosatrienoic acids (EET) and related epoxy fatty acids (EpFA) are endogenous anti-inflammatory compounds, which are converted by the soluble epoxide hydrolase (sEH) to dihydroxylethersatrienoic acids (DHETs) with lessened biological effects. Inhibition of sEH is used as a strategy to increase EET levels leading to lower inflammation. Rheumatoid arthritis is a chronic autoimmune disease that leads to destruction of joint tissues. This pathogenesis involves a complex interplay between the immune system, and environmental factors. Here, we investigate the effects of inhibiting sEH with 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) on a collagen-induced arthritis model. The treatment with TPPU ameliorates hyperalgesia, edema, and decreases the expression of important pro-inflammatory cytokines of Th1 and Th17 profiles, while increasing Treg cells. Considering the challenges to control RA, this study provides robust data supporting that inhibition of the sEH is a promising target to treat arthritis.
PubMed ID: 32400048
MeSH Terms: Animals; Arthritis, Experimental/chemically induced; Arthritis, Experimental/drug therapy; Arthritis, Experimental/immunology*; Arthritis, Experimental/pathology; Collagen/toxicity; Epoxide Hydrolases/antagonists & inhibitors*; Inflammation/etiology; Inflammation/pathology; Inflammation/prevention & control*; Male; Mice; Mice, Inbred DBA; Phenylurea Compounds/pharmacology*; Piperidines/pharmacology*; T-Lymphocytes, Regulatory/drug effects; T-Lymphocytes, Regulatory/immunology*