CATERPILLER proteins contain N-terminal effector domains, a nucleotide binding domain and a series of leucine rich repeats. These proteins are important in immune responses and disease associations have been linked to several, including MHCT2A, ClAS and NOD2/CARD15. Mutations in NOD2/CARD15 are associated exclusively with a subset of Crohn's disease patients. Crohn's disease and ulcerative colitis are complex and chronic disorders that are referred to as inflammatory bowel disease (IBD). Current dogma suggests that IBD results from aberrant immune responses to endemic microflora of the gut. We screened the expression profile of several novel CATERPILLER genes to determine if these genes were influenced in a mouse model for IBD. 16.1/NOD27 was shown to be upregulated ( approximately 100 fold) in the colon and cecum of ILl0-/-mice reared under SPF conditions relative to GF animals. Upregulation of 16.1/NOD27 correlated with spontaneous ex vivo IL-12 secretion of the transverse colon. Biochemical analysis of 16.1/NOD27 has shown it to be a regulator of NF-K B dependent gene expression. These data suggest a role for 16.1/NOD27 in the inflammatory response associated with active colitis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DK069035-02
Application #
7109389
Study Section
Special Emphasis Panel (ZRG1-F07 (20))
Program Officer
Podskalny, Judith M,
Project Start
2005-07-01
Project End
2007-06-30
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
2
Fiscal Year
2006
Total Cost
$50,428
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Davis, Beckley K; Roberts, Reid A; Huang, Max T et al. (2011) Cutting edge: NLRC5-dependent activation of the inflammasome. J Immunol 186:1333-7