Molecular Characterization of the Onset and Progression of Colitis in Inoculated Interleukin-10 Gene-Deficient Mice: A Role for PPARalpha.
The interleukin-10 gene-deficient (Il10(-/-)) mouse is a model of human inflammatory bowel disease and Ppara has been identified as one of the key genes involved in regulation of colitis in the bacterially inoculated Il10(-/-) model. The aims were to (1) characterize colitis onset and progression using a histopathological, transcriptomic, and proteomic approach and (2) investigate links between PPARalpha and IL10 using gene network analysis. Bacterial inoculation resulted in severe colitis in Il10(-/-) 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-old Il10(-/-) mice. Gene expression changes in 12-week-old Il10(-/-) mice were related to PPARalpha signaling likely to control colitis, but how PPARalpha activation might regulate intestinal IL10 production remains to be determined.
Knoch
Bianca
B
Food, Metabolism & Microbiology Section, Food & Textiles Group, AgResearch Grasslands, Tennent Drive, Palmerston North 4442, New Zealand.
Barnett
Matthew P G
MP
Cooney
Janine
J
McNabb
Warren C
WC
Barraclough
Diane
D
Laing
William
W
Zhu
Shuotun
S
Park
Zaneta A
ZA
Maclean
Paul
P
Knowles
Scott O
SO
Roy
Nicole C
NC