Molecular Characterization of the Onset and Progression of Colitis in Inoculated Interleukin-10 Gene-Deficient Mice: A Role for PPARα

Abstract

The interleukin-10 gene-deficient (Il10-/-) mouse is a model of human inflammatory bowel disease andPparahas been identified as one of the key genes involved in regulation of colitis in the bacterially inoculatedIl10-/-model. The aims were to (1) characterize colitis onset and progression using a histopathological, transcriptomic, and proteomic approach and (2) investigate links between PPARαand IL10 using gene network analysis. Bacterial inoculation resulted in severe colitis inIl10-/-mice from 10 to 12 weeks of age. Innate and adaptive immune responses showed differences in gene expression relating to colitis severity. Actin cytoskeleton dynamics, innate immunity, and apoptosis-linked gene and protein expression data suggested a delayed remodeling process in 12-week-oldIl10-/-mice. Gene expression changes in 12-week-oldIl10-/-mice were related to PPARαsignaling likely to control colitis, but how PPARαactivation might regulate intestinal IL10 production remains to be determined.