In a new study published in the Journal of Leukocyte Biology,
researchers from the University of Geneva discovered a new way to reduce inflammation associated with autoimmune diseases like Crohn’s disease, arthritis, and psoriasis. Salt-inducible kinase (SIK) activity is involved in multiple body processes, but this study shows that inhibiting these enzymes in specific cases could reduce the impact of chronic inflammation.
Crohn’s disease (CD) was first described in 1932 as an inflammatory bowel disease characterized by chronic inflammation of the gastrointestinal (GI) tract. CD usually occurs at the end of the ileum and the beginning of the large intestine, affecting the entire thickness of the GI tract wall. Patches of diseased intestine are also common, and patients diagnosed with CD often experience persistent diarrhea, rectal bleeding, abdominal pain, and constipation. Scientists do not know much more about the cause of CD other than connections to heredity, genetic mutations, and environmental factors.
Arthritis, on the other hand, is the leading cause of disability in America, characterized by a spectrum of joint diseases that appear in more than 100 different types and affect 50 million adults. Psoriasis is another autoimmune disease that causes patches of abnormal skin to appear, usually on the elbows, knees or scalp. Psoriasis is not contagious, and there are also several types: Different types: plaque psoriasis (most common), guttate, inverse, pustular, and erythrodermic (most severe).
In their study of two “structurally unrelated” inhibitors of SIK activity, researchers performed genetic interference (RNAi) tests to see what impact there would be on inflammation. They found that inhibiting salt-inducible kinase halts proinflammatory cytokine production and increases anti-inflammatory cytokine secretion by cultured human myeloid cells: monocytes, macrophages, and dendritic cells.
The researchers saw SIK-inhibitors resolving inflammation by preventing the interaction of SIK with TLR signaling. Usually this signaling limits the production of macrophages that produce interleukin-10, an anti-inflammatory molecule, and reduce levels of proinflammatory cytokine interleukin-12 and others.
"This work has the potential to add a new class of therapeutics for inflammatory disorders that could be used in combination with other distinct therapies in hard-to-treat autoimmunity inflammatory conditions,” said Deputy Editor of the Journal of Leukocyte Biology,
John Wherry, PhD.
Now that scientists have an understanding about the anti-inflammatory capabilities of SIK-inhibitors, new drug candidates can be tested in animal models of chronic inflammation and autoimmune disease.
Sources: Crohn’s & Colitis Foundation of America
, Arthritis Foundation
, National Psoriasis Foundation
, Federation of American Societies for Experimental Biology