LONG-TERM EXPOSURE OF MONOCYTES TO PROSTAGLANDIN E2 DESENSITIZES E-PROSTANOID RECEPTOR-2 (EP2): EVIDENCE TOWARDS A PHOSPHORYLATION-INDEPENDENT MECHANISM

CABRERIZO G

Congreso; Congreso SAI; 2019

Prostaglandin E2 (PGE2) is known to inhibit activation of monocytes. Paradoxically, we demonstrated that long-term exposure of monocytes to PGE2 increased their ability to produce LPS-induced TNF. This effect was explained by disruption of the negative feedback elicited by endogenous PGE2 due to desensitization of E-prostanoid receptor-2 (EP2), a G protein-coupled receptor. We aim to study the mechanism of EP2 desensitization in monocytes.Monocytes purified from peripheral blood were cultured for 15 hours in the presence of PGE2 (10-8M), or not (control), and then stimulated with LPS (25 ng/ml). TNF was evaluated by flow cytometry. Addition of a second pulse of PGE2 (10-7M, together with LPS stimulation) led to inhibition of TNF production in control cultures but not in PGE2-pre-treated (desensitized) cultures: 15 +/- 11 vs 66 +/- 9% TNF+ cells (n=7, p