Human, Mouse Studies Suggest MicroRNA Has Potential to Treat Crohn’s Disease, Ulcerative Colitis

Human, Mouse Studies Suggest MicroRNA Has Potential to Treat Crohn’s Disease, Ulcerative Colitis

Synthetic versions of a specific microRNA produced by white blood cells can reduce intestinal inflammation in mice, suggesting a new therapeutic approach to treating Crohn’s disease and ulcerative colitis, according to researchers at the University of Colorado-Anschutz Medical Campus.

Their study, “Myeloid-derived miR-223 regulates intestinal inflammation via repression of the NLRP3 inflammasome,” recently appeared in the Journal of Experimental Medicine.

The team discovered that the microRNA, called miR-223, was present in higher than normal levels in tissue samples from patients with active inflammatory bowel disease (IBD). Researchers noted the same thing in mouse models of gut inflammation.

MicroRNAs are molecules that act to control gene activity, and miR-233 was found in immune cells called neutrophils and monocytes. Earlier research has shown that the molecule blocks the production of NLRP3, a protein that is part of a cell complex called the inflammasome. Researchers believe that IBD results when the body produces an exaggerated immune response towards gut bacteria.

The inflammasome is part of that response. When activated, the cell complex turns on the production of interleukin (IL)-1beta and IL-18. These inflammatory signaling molecules IL-1β attract more white blood cells to the gut in a downward spiral of events.

To test whether the microRNA is really involved in gut inflammation, the team engineered a mouse lacking miR-223. These mice had higher levels of NLRP3, produced more IL-1beta and easily developed gut inflammation.

But when they treated mice with nanoparticles that triggered the production of miR-233, the reverse situation emerged — mice had less NLRP3 and IL-1beta.

“Our study highlights the miR-223-NLRP3-IL-1β regulatory circuit as a critical component of intestinal inflammation,” Eóin McNamee, the study’s senior author, said in a press release. McNamee added that “miR-223 serves to constrain the level of NLRP3 inflammasome activation and provides an early brake that limits excessive inflammation. Genetic or pharmacologic stabilization of miR-223 may hold promise as a future novel therapy for active flares in IBD.”

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