Inflammation is supposed to be a short-term response to an infection or other irritant in the body that is essential to eliminating it. But when inflammation persists, it can contribute to a myriad of common conditions, from cancer to cardiovascular disease.
In their quest to determine just how chronic inflammation of our large intestines, or colon, enables cancer, a scientific team led by Dr. Kebin Liu at the Medical College of Georgia and Georgia Cancer Center at Augusta University has found it turns one more protective mechanism against us and silences another.
Pathway - Cancer - Journal - Cell - Reports
The pathway to cancer they delineated in the journal Cell Reports goes like this: The chronic inflammation of ulcerative colitis prompts high levels of myeloid-derived suppressor cells, or MDSCs, to accumulate in the colon. High levels of MDSCs, in turn, produce higher levels of IL-10, a cytokine known to suppress inflammation. But at this high level, the function of IL-10, like the environment in the colon, changes. IL-10 instead activates STAT3, a protein that works as a gene regulator, which in turn increases expression of two genes -- DNMT1 and DNMT3b -- in the colon. These genes alter the DNA of and ultimately silence a tumor suppressor called interferon regulator factor 8, or IRF8.
Liu notes that the pathway they found that ends with silencing IRF8, likely is not a factor for non-colitis associated colon cancer.
Steps - Ways - Expression - IL-10 - Colon
Next steps include finding ways to inhibit high expression of IL-10 in the colon.
"IL-10 has a dual function. It can either be promoting or interfering with an immune response," says Liu. "What we found here is IL-10 promotes colon cancer."
State - IL-10 - IRF8 - Interaction - Work
In a healthy state, IL-10 and IRF8 have no known interaction but both work in different ways to protect against invaders, says Liu, a cancer immunologist in the MCG Department of Biochemistry and Molecular Biology.
The scientists set...
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