A team, including researchers from the Washington State University Health Sciences Spokane, has identified a novel therapeutic target for treating gout, a common type of arthritis that causes episodes of stiff and painful joints. Their study suggests that blocking a signaling molecule named ‘TAK1’ can suppress inflammation caused by gout. The research paves the way for the development of potential new treatment techniques that could substantially enhance the quality of life of millions of people worldwide suffering from the condition, out of which 8.3 million people or nearly 4 percent of the population are from the United States only. The team’s work has been published in the journal Cellular and Molecular Immunology.
Gout is caused by a high level of uric acid in the blood, which is a natural waste product generated during the digestion of foods that consist of purines, such as red meat, seafood, beer, and dried beans. Increased levels of uric acid can also lead to the creation of monosodium uric acid (MSU) crystals, which can get accumulated in the joints. The immune system sees these crystals as a threat and launches an immune response to increase the interleukin-1-beta (IL-1-beta) production, a cytokine protein that can cause inflammation, triggering intense pain, and swelling. Senior author on the study Salah-Uddin Ahmed, a professor of pharmaceutical sciences in the WSU College of Pharmacy and Pharmaceutical Sciences, says that it is a vicious cycle that begins with the crystals, which result in the production of IL-1-beta, inducing inflammation and activating several other proteins, causing more inflammation. TAK1, one of the proteins activated by IL-1-beta, was what the research team focused on, whereby their initial study showed that it had a vital role in the regulation of IL-1-beta inflammation in rheumatoid arthritis.
They worked towards identifying the molecular mechanism employed by MSU crystals in the production of IL-1-beta inflammation and the role of the protein in the process. With two different cell lines of human macrophages, immune cells vital for inflammation, they discovered that MSU crystals were able to directly trigger TAK1 and other proteins that were previously known to be dependent on the IL-1-beta signaling for activation. They also showed that using a chemical that restrains TAK1 could entirely suppress any inflammation triggered by MSU crystals, both in a rodent model of gout and healthy human macrophage cells.