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

被引：30

作者：

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. ^{[4
]}

Martins Montalli, Victor Angelo ^{[1
]}

Hammock, Bruce D. ^{[3
,5
]}

Napimoga, Marcelo H. ^{[1
]}

机构：

[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] State Univ Londrina UEL, Biol Sci Ctr, Dept Pathol Sci, Londrina, Parana, Brazil

[5] EicOsis LLC, Davis, CA USA

来源：

FASEB JOURNAL | 2020年 / 34卷 / 07期

基金：

巴西圣保罗研究基金会;

关键词：

rheumatoid arthritis; soluble epoxide hydrolase; TPPU; Th1; Th17; Treg; MODIFYING ANTIRHEUMATIC DRUGS; ENDOPLASMIC-RETICULUM STRESS; RHEUMATOID-ARTHRITIS; THERAPEUTIC TARGET; FATTY-ACID; TH17; CELLS; PAIN; INFLAMMATION; PREVALENCE; EXPRESSION;

D O I：

10.1096/fj.202000415R

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：9074 / 9086

页数：13

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[1] Mechanisms of human FoxP3+ Treg cell development and function in health and disease [J].