Retinoic Acid Receptor Alpha And Retinoid X Receptor Alpha Status In Human Ulcerative And Murine Colitis

OBJETIVE: The major purpose of this work was to study the expressions of retinoic acid receptor alpha(RAR-?) and retinoid X receptor alpha(RXR-?) in human ulcerative, murine colitis and the mechanism of therapeutic efficacy of all-trans retinoic acid(ATRA) in Dextran Sulfate Sodium(DSS) induced colitis.METHODS: We utilized colonic tissue from patients with ulcerative colitis(UC),acute DSS models of murine colitis and RAW264.7 cells stimulated with lipopolysaccharide(LPS). The mice were daily given 3%(w/v) DSS to induce murine colitis and treated with different doses of ATRA(100 ?g or 500 ?g) intragastrically until killed on day seven. RAW264.7 cells were treated with ATRA for 1 h earlier than stimulation with LPS. The expressions of RAR-? and RXR-? were checked in human ulcerative, murine colitis and macrophages stimulated with LPS. The changes of pro-inflammatory cytokines, RAR-? and RXR-? were examined after administration of ATRA in macrophages and murine colitis.RESULTS: The expressions of RAR-? and RXR-? were significantly downregulated in human ulcerative, murine colitis and macrophages stimulated with LPS. Receptors downregulation was connected with an increase of the expressions of pro-inflammatory cytokines. ATRA administration downregulated pro-inflammatory cytokines expressions and induced RAR-? expression in vitro and in vivo. ATRA administration also induced RXR-? expression in vivo.CONCLUSIONS: The reduction of RAR-? and RXR-? may be associated with the ulcerative colitis occurrence and development. ATRA may have a anti-inflammatory effect by restoring RAR-? and RXR-? expressions in vivo, and could be used as a new therapy in ulcerative colitis.