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068 CDP/CUX IS NECESSARY FOR BALANCED REGULATION OF INFLAMMATORY MOLECULES EXPRESSION DURING MOUSE EXPERIMENTAL COLITIS M Darsigny, F Boudreau Recent studies have suggested that CDP/Cux regulates normal haematopoiesis as well as genes associated with the inflammatory response. However, the role played by this transcription factor during inflammatory stress in unknown. CDP/Cux mutant mice have shown alterations in the expression of the small intestinal specific gene sucrase-isomaltase in colonocytes.
Département d'anatomie et biologie cellulaire, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Quebec
AIM: Since modification of colonocyte identity can lead to pathological conditions, we sought to determine the role played by CDP/Cux during colonic mucosa inflammatory response.
METHODS: CDP/Cux mutant mice were challenged with a 7 days treatment of 2.5% dextran sodium sulphate (DSS) in drinking water after which animals were sacrificed and assessed for clinical manifestation of disease (stools aspect, rectal bleeding and colon length), histological alterations and mRNA expression levels of various cytokines and chemokines.
RESULTS: The detailed analysis of clinical criteria associated with intestinal colitis confirmed a greater disease activity in CDP/Cux mutant mice. To better understand the inflammatory cascade that could have led to these clinical findings, we measured the expression of diverse inflammatory molecules by real-time PCR analysis. The expression of TNF, IL-1b, TGF-b and IFNg were significantly higher in the DSS-treated mutant group compared to controls. In addition, some chemokines, like CXCL1 and CCL3, were also induced in this group.
CONCLUSION: Our results demonstrate that the loss of CDP/Cux transcription factor is associated with a significant increase in colonic disease severity. This could have been caused by inappropriate inflammatory molecule expression during the DSS-induced colitis. Current investigations are in process to characterize the transcriptional role played by CDP/Cux in this context.
This work was supported by CIHR, NSERC, CRS, CFI and FRSQ