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UNC Researchers Reduce Arthritis Severity By Turning Off Molecular Switch

CHAPEL HILL, N.C. --In a scientific first, researchers at the University of North Carolina at Chapel Hill have reduced the severity of arthritis by turning off a molecular switch, a gene called NF-kappa B.

A report published Nov. 10 in the Proceedings of the National Academy of Sciences says the findings, based on experiments in laboratory rats, establish an important molecular mechanism in human rheumatoid arthritis. The findings demonstrate the feasibility of new ways to treat the disease, including gene therapy.

"These findings underscore NF-kappa B as a very attractive target for arthritis treatments, including a new generation of drugs targeted specifically to the molecule," says the team's leader, Dr. Sergei S. Makarov, research assistant professor of medicine at the UNC-CH School of Medicine and the Thurston Arthritis Research Center.

"In rheumatoid arthritis, the delicate synovial joint lining dramatically expands and transforms into an aggressive, tumor-like structure that invades and erodes the joint," Makarov says. "We started studying the role for NF-kappa B in arthritis because it controls the expression of numerous inflammatory genes, and we knew that it's activated within the arthritic synovium. Around that time, our collaborator, Dr. Al Baldwin, published his pioneer study demonstrating that activated NF-kappa B is needed to protect cancer cells in vitro from apoptosis, or programmed cell death."

From their subsequent in vitro studies, Makarov and his colleagues learned that similar mechanisms might operate in rheumatoid arthritis. "We found that inflammatory stimuli caused activation of NF-kappa B inside the cells from arthritic joints, rendering them resistant to apoptosis. It seemed that the more inflammation you had, the more protected those cells were against apoptosis," he says.

"We then predicted that if you block NF-kappa B in the arthritic joint, inflammation would go down, the cells would no longer be protected ag
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Contact: Lynn Wooten
lwooten.est1@mail.unch.unc.edu
919-966-6046
University of North Carolina School of Medicine
2-Nov-1998


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