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Division of Arthritis Research, The Scripps Research Institute, La Jolla, CA 92037
IL-18, a cytokine originally identified as IFN-
-inducing factor,
is a member of the IL-1 family of proteins. Because IL-1
and IL-1ß
are important mediators in the pathogenesis of arthritis, the present
study addresses the expression of IL-18 and its role in regulating in
articular chondrocytes. IL-18 mRNA was induced by IL-1ß in
chondrocytes. Chondrocytes produced the IL-18 precursor and in response
to IL-1 stimulation secreted the mature form of IL-18. Studies on IL-18
effects on chondrocytes showed that it inhibits TGF-ß-induced
proliferation and enhances nitric oxide production. IL-18 stimulated
the expression of several genes in normal human articular chondrocytes
including inducible nitric oxide synthase, inducible cyclooxygenase,
IL-6, and stromelysin. Gene expression was associated with the
synthesis of the corresponding proteins. Treatment of normal human
articular cartilage with IL-18 increased the release of
glycosaminoglycans. These finding identify IL-18 as a cytokine that
regulates chondrocyte responses and contributes to cartilage
degradation.
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