Soluble epoxide hydrolase inhibitor, TPPU, increases regulatory T cells pathway in an arthritis model

Autor(es)

Trindade-da-Silva, Carlos A. ^[1] ; Clemente-Napimoga, Juliana T. ^[1] ; Abdalla, Henrique B. ^[1] ; Rosa, Sergio Marcolino ^[1] ; Ueira-Vieira, Carlos ^[2] ; Morisseau, Christophe ^[3] ; Verri Jr, Waldiceu A. ; Martins Montalli, Victor Angelo ^[1] ; Hammock, Bruce D. ^{[3, 4]} ; Napimoga, Marcelo H. ^[1]

Afiliação do(s) autor(es)

^[1] Inst Sao Leopoldo Mandic, Fac Sao Leopoldo Mandic, Lab Neuroimmune Interface Pain Res, R Jose Rocha Junqueira 13, BR-13045755 Campinas, SP - Brazil

^[2] Univ Fed Uberlandia, Inst Biotechnol, Lab Genet, Uberlandia, MG - Brazil

^[3] Univ Calif Davis, UC Davis Comprehens Canc Ctr, Dept Entomol & Hematol, Davis, CA 95616 - USA

^[4] EicOsis LLC, Davis, CA - USA

• Tipo de documento: Artigo Científico
• Fonte: FASEB JOURNAL; v. 34, n. 7 MAY 2020.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 17/22334-9 - Uso de sistemas de liberação de fármacos para o desenvolvimento e aplicabilidade de agentes anti-inflamatórios com potencial efeito imunomodulador e neuroprotetor
• Beneficiário: Marcelo Henrique Napimoga
• Modalidade de apoio: Auxílio à Pesquisa - Temático