Exogenous fatty acids and niacin on acute prostaglandin D2 production in human myeloid cells

Abstract

Niacin activates HCA2 receptor that results in the release of PGD2. However, little is known on PGD2-producing cells and the role of fatty acids. Notably M-CSF macrophages exhibited a timely dependent PGD2 production upon niacin challenge. Short pretreatment of M-CSF macrophages with autologous postprandial TRLs induced the down-regulation of HCA2 gene and up-regulation of genes encoding COX1 and COX2 enzymes in a fatty acid-dependent manner. These effects were paralleled by a higher PGD2 production with postprandial TRL-SFAs. The niacin-mediated transcriptional activity of all genes involved in PGD2 biosynthesis was desensitized in a time-dependent manner by postprandial TRLs, leading to a decreased PGD2 release. In vivo, the net excursions of PGD2 in plasma followed similar fatty acid-dependent patterns as those found for PGD2 release in vitro. The predominant fatty acid class in the diet acutely modulates PGD2 biosynthetic pathway both in vitro and in vivo.