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G PROTEINS KEY IN ARTHRITIC INFLAMMATION

By Fred Henahan, Access Excellence


SAN FRANCISCO- SAN FRANCISCO- New findings from Johns Hopkins University researchers suggest G-proteins are a key link in the chain reaction that causes inflammation of the lining of the joints in arthritis. The discovery may aid the search for drugs that suppress or control these events before the joints are damaged, according to the researchers who presented at the 59th Annual Scientific Meeting of American College of Rheumatology's in San Francisco.

The scientists found that activation of two types of molecules called G-proteins is part of a cascade of signals that causes the lining of the joints to become inflamed. The reaction begins when bradykinin, a small protein, binds with special receptors on the outside of the cells making up the lining of the joints. The G-proteins are in the cellular "skin" of this lining, called the synovium, which is rich in bradykinin receptors.

"This study provides the first direct evidence that G-proteins connect the pathways to bradykinin receptors in human synovial cells," says Helen Robinson, M.D., the study's lead author. "Now the goal is to develop strategies to block the pathways and to develop new anti-inflammatory drugs that can do that job." Currently available anti-inflammatory drugs generally have been disappointing, making it logical to investigate other ways to prevent or control inflammation, Robinson says.

When bradykinin binds with its receptors, also found throughout the body, the G-proteins are activated and act as messengers that pass the signal to the inside of the synovial cells and trigger inflammation, says Robinson. In the study, Hopkins scientist s used cells from the knees of people with rheumatoid arthritis and measured the process by tracking the rise in calcium levels in synovial cells, which occurs after they have been stimulated.

Rheumatoid arthritis, an autoimmune disorder in which the immune system attacks the body's own tissues, causes the joints to become painful, swollen, stiff and sometimes deformed. It usually starts in early adulthood or middle age but can develop at any age. It affects two to three times more women than men. Chronic inflammation in arthritis destroys the cartilage, underlying bone and eventually the joint.


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