Platelet-activating factor downregulates the expression of liver X receptor-[alpha] and its target genes in human neutrophils

• Published in: The FEBS journal 2014-02, Vol.281 (3), p.970
• Main Authors: Reyes-Quiroz, María E, Alba, Gonzalo, Santa-Maria, Consuelo, Saenz, Javier, Geniz, Isabel, Jimenez, Juan, Ramirez, Remedios, Martin-Nieto, José, Pintado, Elizabeth, Sobrino, Francisco
• Format: Article
• Language: English
• Subjects: Blood platelets; Gene expression; Leukocytes; Ligands; Molecular biology
• ISSN: 1742-464X; 1742-4658
• DOI: 10.1111/febs.12662

Liver X receptors (LXRs) are ligand-activated members of the nuclear receptor superfamily that regulate the expression of genes involved in lipid metabolism and inflammation, although their role in inflammation and immunity is less well known. It has been reported that oxysterols/LXRs may act as anti-inflammatory molecules, although opposite actions have also been reported. In this study, we investigated the effect of platelet-activating factor (PAF), a proinflammatory molecule, on LXR[alpha] signalling in human neutrophils. We found that PAF exerted an inhibitory effect on mRNA expression of TO901317-induced LXR[alpha], ATP-binding cassette transporter A1, ATP-binding cassette transporter G1, and sterol response element binding protein 1c. This negative action was mediated by the PAF receptor, and was dependent on the release of reactive oxygen species elicited by PAF, as it was enhanced by pro-oxidant treatment and reversed by antioxidants. Current data also support the idea that PAF induces phosphorylation of the LXR[alpha] molecule in an extracellular signal-regulated kinase 1/2-mediated fashion. These results suggest that a possible mechanism by which PAF exerts its proinflammatory effect is through the downregulation of LXR[alpha] and its related genes, which supports the notion that LXR[alpha] ligands exert a modulatory role in the neutrophil-mediated inflammatory response. [PUBLICATION ABSTRACT]