Targeting P-selectin glycoprotein ligand 1 in preclinical ARDS: Genetic and epigenetic regulation of the promoter.

We previously identified a missense single nucleotide polymorphism rs2228315 (G>A, Met62Ile) in the selectin-P-ligand gene (), encoding P-selectin glycoprotein ligand 1 (PSGL-1), to be associated with increased susceptibility to acute respiratory distress syndrome (ARDS). These earlier studies demonstrated that lung tissue expression was increased in mice exposed to lipopolysaccharide (LPS)- and ventilator-induced lung injury (VILI) suggesting that inflammatory and epigenetic factors regulate promoter activity and transcription. In this report, we used a novel recombinant tandem PSGL1 immunoglobulin fusion molecule (TSGL-Ig), a competitive inhibitor of PSGL1/P-selectin interactions, to demonstrate significant TSGL-Ig-mediated decreases in lung tissue expression as well as highly significant protection from LPS- and VILI-induced lung injury.