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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 an intracellular binding site. They increase PGE2- induced Gs- mediated formation of cAMP and thereby promote anti- inflammatory signaling of EP4. In addition, SPMs endow the In the absence of the EP4 receptor, SPMs lose their anti- inflammatory and pro- resolving activity in vitro and in vivo. Our findings reveal an unusual mechanism of allosteric receptor and anti- inflammatory effects, which may facilitate approaches to treat inflammation.
