Researchers already knew that heightened levels of the immune molecule IL-17 are associated with the worst symptoms of IBD. But while drugs targeting IL-17 have been developed for psoriasis, they have been ineffective at treating IBD; they also pose the problem of impacting immune cells throughout the body.
In the new study, Dr. Poojary and his colleagues probed what other molecules interact in the inflammatory cells that produce IL-17 in the gut. Their experiments turned up a protein called Pak2. When the researchers blocked Pak2 in mice, the animals lost weight, had more colon inflammation, and showed other symptoms of IBD, including diarrhea and blood in their stools. In the presence of Pak2, however, the IBD-like inflammation eased.
Coping with Inflammatory Bowel Disease
Further experiments revealed that Pak2 binds to RORgt, a protein that activates the IL-17 gene. But while RORgt acts like an accelerator for inflammation by boosting levels of IL-17, Pak2 acts like the brakes. Dr. Poojary’s team showed that Pak2 acts to degrade RORgt and prevent it from activating the IL-17 gene.
His lab is now planning follow-up studies to develop drugs that could encourage the Pak2 brakes on inflammation. The research could have implications beyond IBD, he added.
“Although we studied this in the context of bowel diseases, we think this pathway is probably also applicable to other inflammatory diseases including multiple sclerosis and rheumatoid arthritis,” he said.
Source: Eurekalert
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