Study traces chemotherapy-induced diarrhea to immune cells

Source: Xinhua| 2018-06-27 05:12:39|Editor: Mu Xuequan
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CHICAGO, June 26 (Xinhua) -- A research in mice at Washington University School of Medicine in St. Louis indicates that specialized immune cells called macrophages can trigger intestinal contractions independent of the nervous system, thus inducing diarrhea.

Researchers at the university focused on a receptor on macrophages called TRPV4. These receptors are important to contractions in the gut.

"We found that the macrophages themselves trigger muscle contractions in the gut without any involvement from neurons," said co-senior investigator Hongzhen Hu, an associate professor of anesthesiology at the university. "The pathway works in an entirely different way from what we had expected."

In experiments involving genetically modified mice, the researchers found that animals without TRPV4 receptors on gut macrophages had poor intestinal motility. They also found that by inhibiting the actions of these receptors, they could reverse diarrhea caused by chemotherapy drugs.

"Solving problems with bowel function in chemotherapy patients is important because at least half of those patients develop diarrhea, but we'd also like to see whether these receptors on macrophages can be targeted to treat irritable bowel syndrome, which often doesn't respond well to existing drugs," said co-senior investigator Brian S. Kim, assistant professor of medicine in the Division of Dermatology at the university.

Previously, the researchers had identified a role for macrophages' TRPV4 receptors in chronic itching in the skin. In this study, they focused on macrophages that reside in the gut's smooth muscle layer, demonstrating that the receptors sense heat, chemical changes and the movement of food through the intestine. All of those things can trigger muscle contractions, or motility, in the gut.

The research may provide a new target to help treat chemotherapy-induced diarrhea, and potentially diarrhea linked to other GI problems.

The findings were published on June 17 in the journal Immunity.