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THE C/EBPbeta TRANSCRIPTION FACTOR REGULATES INTESTINAL INFLAMMATION
C Asselin, N Turgeon, M BlaisDépartement d'anatomie et biologie cellulaire, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, QC
Aims: The C/EBPbeta transcription factor regulates the intestinal epithelial cell (IEC) inflammatory response, and controls the differentiation of immune cells, including macrophages and granulocytes. We hypothesize that C/EBPbeta is an important regulator of intestinal inflammation in vivo.
Methods: Colitis was induced in control, C/EBPbeta global or intestinal-specific knockout mice by adding 3.5% DSS to the drinking water. Proximal and distal colons were harvested after six days. Severity of colitis was assessed by the Disease Activity Index (DAI), with parameters including body weight, stool consistency, fecal blood loss and colon length, and by histological criteria. The presence of inflammatory cells was determined by immunofluorescence with antibodies against the immune cell marker CD4. Inflammatory gene expression was assessed by semi-quantitative RT-PCR analysis, with total distal colon RNAs.
Results: C/EBPbeta-deficient mice did not display apparent signs of intestinal inflammation at the basal level. However, C/EBPbeta knockout mice were more sensitive to DSS treatment, as determined by DAI and histological criteria. C/EBPbeta -/- mice showed decreased recovery and increased mortality after the end of DSS treatment. Increased recruitment of CD4+ immune cells was observed. Aggravated C/EBPbeta-deficient mice colitis symptoms correlated with increased expression of inflammatory genes, such as Il6, Il17, Ifngamma, Il12b, Il22, Tnfalpha, Icos and Cxcl1. Finally, IEC-specific C/EBPbeta-deficient mice showed increased inflammatory manifestations.
Conclusions: C/EBPbeta regulates intestinal inflammation by affecting both the resolution and the duration of the inflammatory response. In addition, IEC-specific C/EBPbeta may contribute to the intensity of colitis manifestations. Supported by CCFC.