SPMs exert anti-inflammatory and pro-resolving effects through positive allosteric modulation of the prostaglandin EP4 receptor.

ABSTRACT: Inflammation is a protective response to pathogens and injury. To be effective it needs to be resolved by endogenous mechanisms in order to avoid prolonged and excessive inflammation, which can become chronic. Specialized pro-resolving mediators (SPMs) are a group of lipids derived from omega-3 fatty acids, which can induce the resolution of inflammation. How SPMs exert their anti-inflammatory and pro-resolving effects is, however, not clear. Here, we show that SPMs such as protectins, maresins, and D-series resolvins function as biased positive allosteric modulators (PAM) of the prostaglandin E₂ (PGE₂) receptor EP4 through an intracellular binding site. They increase PGE₂-induced G_s-mediated formation of cAMP and thereby promote anti-inflammator

SUBMITTER: Alnouri MW 

PROVIDER: S-EPMC11474063 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature