The Endocannabinoid Metabolite Prostaglandin E2 (PGE2)-Glycerol Inhibits Human Neutrophil Functions: Involvement of Its Hydrolysis into PGE2 and EP Receptors

摘要: The endocannabinoids 2-arachidonoyl-glycerol and N -arachidonoyl-ethanolamine mediate an array of pro- anti-inflammatory effects. These effects are related, in part, to their metabolism by eicosanoid biosynthetic enzymes. For example, can be metabolized cyclooxygenase-2 into PG-ethanolamide (PG-EA) PG-glycerol (PG-G), respectively. Although PGE 2 is a recognized suppressor neutrophil functions, the impact cyclooxygenase-derived such as -EA or -G on neutrophils unknown. This study’s aim was define these mediators functions underlying cellular mechanisms involved. We show that -G, but not -EA, inhibits leukotriene B 4 biosynthesis, superoxide production, migration, antimicrobial peptide release. were prevented EP 1 /EP receptor antagonist AH-6809 ONO-AE2-227. required its hydrolysis , observed with non-hydrolyzable -serinol amide, completely methyl-arachidonoyl-fluorophosphate palmostatin B, partially JZL184 WWL113. we could detect six documented PG-G hydrolases quantitative PCR, only ABHD12 ABHD16A detected immunoblot. Our pharmacological data, combined our protein expression did allow us pinpoint one lipase, rather support involvement uncharacterized lipase and/or multiple hydrolases. In conclusion, human through activating receptor. also indicates regulate inflammation altering balance between PG levels vivo.