IRAK-M: Altered Protein Protects Against Inflammation And Colon Cancer

Modifying the shape of IRAK-M, a protein that controls inflammation, can significantly reduce the clinical progression of inflammatory bowel disease and colon cancer in pre-clinical animal models, Virginia Tech researchers have found.

Interleukin receptor associated kinase M (IRAK-M), the altered protein, causes the immune system to become supercharged, clearing out the bacteria before they can do any damage.

There is a close link between uncontrolled inflammation in the gut associated with inflammatory bowel disease and the eventual development of colon cancer. This uncontrolled inflammation is associated with changes in bacteria populations in the gut, which can invade the mucosal tissue after damage to the protective cellular barrier lining the tissue.

Altered IRAK-M Protein

Coy Allen, an assistant professor of inflammatory disease in the Department of Biomedical Sciences and Pathobiology in the Virginia-Maryland College of Veterinary Medicine and a Fralin Life Science Institute affiliate, said:

“When we tested mice with the altered IRAK-M protein, they had less inflammation overall, and remarkably less cancer.”

Coy Allen

Coy Allen, (left) an assistant professor of inflammatory disease in the Department of Biomedical Sciences and Pathobiology in the Virginia-Maryland College of Veterinary Medicine, and doctoral student Daniel Rothschild prepare reagents to detect and characterize IRAK-M in cells. Credit: Michael Sutphin

The next step, he said, will be to evaluate these findings in human patients through ongoing collaborations with Carilion Clinic and Duke University. The team is also evaluating their findings in laboratory-assembled ‘mini-guts’ — live tissue models that Allen and his team assembled by growing intestinal stem cells on petri dishes to form highly complex small intestinal and colon tissue.

Colon cancer is the second leading cause of cancer-related deaths in the United States and the third most common cancer in men and women, according to the Centers for Disease Control and Prevention.

The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, and grant funding through the Virginia-Maryland College of Veterinary Medicine.

Daniel E. Rothschild et al.
Enhanced Mucosal Defense and Reduced Tumor Burden in Mice with the Compromised Negative Regulator IRAK-M
EBioMedicine (2017). DOI: 10.1016/j.ebiom.2016.11.039

Top Image: a mouse intestinal organoid, or “mini-gut,” used to study epithelial cell barrier function in ongoing inflammatory bowel disease and cancer studies. Photo courtesy of Coy Allen. Credit: Virginia Tech

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