Soluble epoxide hydrolase inhibitor, TPPU, increases regulatory T cells pathway in an arthritis model
Open Access
- 13 May 2020
- journal article
- research article
- Published by Wiley in The FASEB Journal
- Vol. 34 (7), 9074-9086
- https://doi.org/10.1096/fj.202000415r
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.Keywords
Funding Information
- Fundação de Amparo à Pesquisa do Estado de São Paulo (2017/22334‐9)
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (302527/2019‐2)
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (001)
- National Institute of Environmental Health Sciences (R35 ES030443, P42ES04699)
This publication has 50 references indexed in Scilit:
- Phosphorylation of FOXP3 controls regulatory T cell function and is inhibited by TNF-α in rheumatoid arthritisNature Medicine, 2013
- Small molecule inhibitors of RORγt: Targeting Th17 cells and other applicationsEuropean Journal of Immunology, 2012
- Acute augmentation of epoxygenated fatty acid levels rapidly reduces pain-related behavior in a rat model of type I diabetesProceedings of the National Academy of Sciences of the United States of America, 2012
- T-bet employs diverse regulatory mechanisms to repress transcriptionTrends in Immunology, 2012
- Heme oxygenase-1 ameliorates LPS-induced acute lung injury correlated with downregulation of interleukin-33International Immunopharmacology, 2011
- Nucleosides from Phlebotomus papatasi Salivary Gland Ameliorate Murine Collagen-Induced Arthritis by Impairing Dendritic Cell FunctionsThe Journal of Immunology, 2011
- 1-Aryl-3-(1-acylpiperidin-4-yl)urea Inhibitors of Human and Murine Soluble Epoxide Hydrolase: Structure−Activity Relationships, Pharmacokinetics, and Reduction of Inflammatory PainJournal of Medicinal Chemistry, 2010
- Pharmacokinetic screening of soluble epoxide hydrolase inhibitors in dogsEuropean Journal of Pharmaceutical Sciences, 2010
- Foot pain in rheumatoid arthritis prevalence, risk factors and management: an epidemiological studyClinical Rheumatology, 2009
- IL-33 exacerbates antigen-induced arthritis by activating mast cellsProceedings of the National Academy of Sciences of the United States of America, 2008