INHIBITION OF PROSTAGLANDIN E2 SYNTHESIS BY HYALURONAN THROUGH NF-KB DOWN-REGULATION VIA ICAM-1 IN U937 MACROPHAGES

SummaryHyaluronan suppressed lipopolysaccharide-stimulated prostaglandin E2 production via intercellular adhesion molecule-1 through down-regulation of nuclear factor-κB. Administration of hyaluronan into rheumatoid joints may decrease prostaglandin E2 production by activated macrophages, which could result in improvement of arthritic pain.IntroductionProstaglandin E2 (PGE2) is one of the key mediators of inflammation in rheumatoid arthritis (RA) joints. Intra-articular injection of high molecular weight hyaluronan (HA) into RA knee joints relieves arthritic pain. Although HA has been shown to inhibit PGE2 production in cytokine-stimulated synovial fibroblasts, it remains unclear how HA suppresses PGE2 production in catabolically activated cells. Furthermore, HA effect on macrophages has rarely been investigated in spite of their contribution to RA joint pathology.ObjectivesThis study was aimed to investigate the inhibitory mechanism of HA on lipopolysaccharide (LPS)-stimulated PGE2 in U937 human macropha...