A regulatory loop involving the cytochrome P450-soluble epoxide hydrolase axis and TGF-β signaling.

ABSTRACT: Fatty acid metabolites, produced by cytochrome P450 enzymes and soluble epoxide hydrolase (sEH), regulate inflammation. Here, we report that the transforming growth factor β (TGF-β)-induced polarization of macrophages to a pro-resolving phenotype requires Alk5 and Smad2 activation to increase sEH expression and activity. Macrophages lacking sEH showed impaired repolarization, reduced phagocytosis, and maintained a pro-inflammatory gene expression profile. 11,12-Epoxyeicosatrienoic acid (EET) was one altered metabolite in sEH^-/- macrophages and mimicked the effect of sEH deletion on gene expression. Notably, 11,12-EET also reduced Alk5 expression, inhibiting TGF-β-induced Smad2 phosphorylation by triggering the cytosolic translocation of the E3 ligase Smurf2. These findings sugge

SUBMITTER: Li X 

PROVIDER: S-EPMC11466655 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature