Mechanism of action and potential applications of selective inhibition of microsomal prostaglandin E synthase-1-mediated PGE₂ biosynthesis by sonlicromanol's metabolite KH176m.

ABSTRACT: Increased prostaglandin E2 (PGE₂) levels were detected in mitochondrial disease patient cells harboring nuclear gene mutations in structural subunits of complex I, using a metabolomics screening approach. The increased levels of this principal inflammation mediator normalized following exposure of KH176m, an active redox-modulator metabolite of sonlicromanol (KH176). We next demonstrated that KH176m selectively inhibited lipopolysaccharide (LPS) or interleukin-1β (IL-1β)-induced PGE₂ production in control skin fibroblasts. Comparable results were obtained in the mouse macrophage-like cell line RAW264.7. KH176m selectively inhibited mPGES-1 activity, as well as the inflammation-induced expression of mPGES-1. Finally, we showed that the effect of KH176m on mPGES-1 expre

SUBMITTER: Jiang X 

PROVIDER: S-EPMC7806836 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature