Study identifies key protein that drives Liu

Spokane, Washington – Scientists have identified a protein known as sulfatase-2 that plays a key role in the damage caused by rheumatoid arthritis. Rheumatoid arthritis, a chronic disease in which the immune system attacks the body’s own joint tissue, causes , affecting an estimated 1.5 million Americans.

It was published in the magazine cellular and molecular immunology, This finding sheds new light on the molecular processes that drive inflammation seen in rheumatoid arthritis. Also, the day may come when the treatment for this disease, for which there is currently no cure, will be improved.

“Tumor necrosis factor-alpha (TNF-alpha for short) is one of the major inflammatory proteins that causes rheumatoid arthritis and is the target of many currently available therapeutics.” “However, over time, patients may develop resistance to these drugs, meaning they no longer work. That’s why we were looking for a drug target that doesn’t exist, and basically the proteins it interacts with may play a role.”

Sulfatases, such as sulfatase-2, have been extensively studied for their role in various types of cancer, but no one has investigated how they are involved in inflammatory and autoimmune diseases such as rheumatoid arthritis. Ahmed said.

The research team first explored this idea using cells called synovial fibroblasts. Synovial fibroblasts line the joints and keep them lubricated to ensure fluid movement.

“In rheumatoid arthritis, these normally resting cells are activated by TNF-alpha and other inflammatory molecules to assume this aggressive nature,” said first author Ruby J. Siegel. I’m here. “They aren’t dead when they should be, they grow in an almost tumor-like fashion, forming this giant synovial tissue that shouldn’t even be close to their size, while simultaneously activating proteins that destroy cartilage and bone. increase.”

Using joint lining cells from rheumatoid arthritis patients, we depleted sulfatase-2 from one group of cells before stimulating all cells with inflammatory TNF-α. What they found was that cells lacking sulfatase-2 did not display the same exaggerated inflammatory response to TNF-α as cells that were left intact.

“Investigating sulfatase for its potential role in inflammation was an educated guess, but upon investigation, we found a very consistent pattern of increased sulfatase-2 expression across the different tissues and samples examined. I saw it,” Ahmed said. “This indicates that TNF-α is dependent on sulfatase-2 to promote inflammation, because as soon as sulfatase-2 was removed, the inflammatory effects of TNF-α were significantly reduced. is.”

After a series of experiments spanning four years, the researchers’ findings open the door to future animal studies to test the efficacy of inhibiting sulfatase-2 to alleviate symptoms of rheumatoid arthritis. may one day lead to the development of new combination therapies that target sulfatase-2 along with other inflammatory proteins to prevent bone loss, cartilage damage and joint deformity. It may help address the shortcomings of available rheumatoid arthritis drugs. Many of them have serious side effects.

“These drugs block TNF-alpha throughout the body, but they have important immune functions,” Siegel said, adding that patients taking these types of drugs are more susceptible to infections and develop cancer. He added that there is a high risk of terminology. She also said that TNF-α inhibitors do not work for everyone and are not recommended for patients with certain other health conditions.

Funding for this study was provided by the National Institutes of Health and the Rheumatology Research Foundation.

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