The importance of the retinoid X receptor alpha in modulating inflammatory signaling in acute murine colitis.

BACKGROUND: In order for vitamin D to signal and regulate inflammatory pathways, it must bind to its receptor (VDR) which must heterodimerize with the retinoid X receptor alpha (RXRα). Although the role that vitamin D signaling plays in the development and progression of colitis, a disease characterized by excessive inflammation, has been suggested, little research has been done on determining the role that RXRα plays in acute colitis development. AIMS: This study sought to determine the effects that reduced availability of RXRα would have on the development of acute murine colitis. Expression of inflammatory markers, VDR and RXRα were investigated to determine if the reduction in expression of RXRα in RXRα(+/-) mice would result in increased inflammatory signaling and receptor downregulation as compared to their wild-type littermates. METHODS: An acute murine model of colitis, the axozymethane (AOM) and dextran sulfate sodium (DSS) model was utilized in wild-type and RXRα(+/-) mice. Gross manifestations of colitis measured included weight loss and colitis score. Immunblots and real-time PCR were performed for inflammatory markers and receptor expression. RESULTS: RXRα(+/-) mice induced with AOM/DSS colitis demonstrated increased gene expression of Snail and Snail2, transcription factors downstream of inflammatory mediators, as compared to their wild-type littermates. CONCLUSIONS: This demonstrates the importance of RXRα in regulating inflammation in acute colitis and also identifies RXRα expression as a new consideration when developing successful interventions for acute colitis due to the requirement of numerous receptors for RXRα.

Duke Scholars

Author Rebecca W Knackstedt Surgery, Plastic, Maxillofacial, and Oral Surgery