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Feedback loop explains inflammatory effect on intestinal lining
Date:3/18/2010

Signals released by immune cells during a bout of inflammatory bowel disease interfere with intestinal cells' ability to regenerate. Yet people with inflammatory bowel diseases have a significantly higher risk of developing colon cancer: a hyper-activation of growth in those same intestinal cells.

Researchers at Emory University School of Medicine have identified a feedback loop involving a growth-regulating circuit in intestinal cells, which helps explain these apparently contradictory observations. The findings also suggest that interfering with one component of the feedback loopa protein called "dickkopf 1" may aid in controlling inflammatory bowel diseases.

The results are published online and scheduled for publication in the March 26, 2010 issue of the journal Immunity.

Senior author of the paper was Asma Nusrat, MD, Emory professor of pathology and laboratory medicine. The research was conducted by postdoctoral fellows Porfirio Nava, Stefan Koch and Mike Laukoetter. Laukoetter is now at the University of Mnster in Germany.

The cells lining the intestine, or intestinal epithelial cells, are normally able to repair breaks in the lining by dividing and migrating until the wound has been healed, Nusrat explains. In inflammatory bowel diseases such as Crohn's or ulcerative colitis, immune cells release signals that prevent this repair and cause epithelial cells to die.

Nusrat and her colleagues examined mice treated with a chemical, dextran sulfate, which gives them colitis. The most prominent signaling molecules given off by immune cells in inflamed intestinal tissue were the cytokines ("cell movers") interferon-gamma and tumor necrosis factor-alpha. When the researchers treated intestinal cells by themselves in dishes with these cytokines, the cells had a burst of growth but then started to die out after three days.

"We were puzzled when we saw that cytokines induced activation of a pathway that
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Contact: Holly Korschun
hkorsch@emory.edu
404-727-3990
Emory University
Source:Eurekalert

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