PULSE OF PROSTAGLANDIN E2 TRIGGERS GENETIC REPROGRAMMING TO DRIVE HUMAN MONOCYTE-DERIVED MACROPHAGES INTO A PRO-RESOLUTION PROFILE

G. CABRERIZO; V. RAMIREZ; M.C. MONZANI; A. CEBALLOS; F. REMES LENICOV

San Luis

Congreso; LXXI REUNIÓN CIENTÍFICA ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA; 2023

SOCIEDAD ARGENTINA DE INMUNOLOGÍA

Prostaglandin E2 (PGE2) is a lipid mediator with recognized inflammatory properties but, paradoxically, is also critical for the initiation of the resolution of inflammation. Macrophages play a fundamental role in resolution through cytokine secretion and the removal of apoptotic cells. We have previously shown that PGE2 induces in macrophages a unique pro-resolution profile characterized by increased efferocytosis (EC), increased VEGFa expression and resistance to LPS-mediated TNF and IL-6 production.Our study aims to evaluate the mechanism through which PGE2 induces this profile.For this purpose, monocytes were purified from buffy coats and were differentiated into macrophages over 7 days by the addition of M-CSF (50 ng/mL). Macrophages were treated at day 5 of culture with PGE2 (1 μM) until day 7. Control macrophages were cultured without PGE2. EC was quantified by flow cytometry measuring incorporation of CFSE-stained apoptotic Jurkat cells. Transcriptional changes were analyzed by RNAseq and by qRT-PCR.First, we studied PGE2-canonical cAMP-mediated signaling. Treatment with cAMP analog 8-Br-cAMP and with EP4 receptor agonist L-902,688 (n=5, p