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mcith_OSTEOARTHRITIS.JPG Following is the 3d structure of IL-1 receptor taken from pdb. This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2.

(Click image to enlarge)

Overview: Osteoarthritis is a degenerative disease of cartilage by which almost 80% of the population above 40 years is being affected. Cartilage is the tough elastic material that covers and protects the ends of bones. In healthy joints cartilage acts as a shock absorber when you put weight on the joint. The two major components of cartilage are proteoglycan and type II collagen which are produced by chondrocytes. The primary enzymes responsible for the degradation of cartilage are the matrix metalloproteinase's (MMPs). These enzymes are secreted by both synovial cells and chondrocytes and are categorized into three general categories: a) collagenases b) stromelysins and, c) gelatinases. They are secreted as inactive proenzymes that require enzymatic cleavage in order to become activated, stromelysin serve as an activator for its own proenzyme, as well as for procollagenase and prostromelysin, thus creating a positive feedback loop of proMMP activation in cartilage. Interleukin-1 (IL-1). IL-1 is a potent pro-inflammatory cytokine that is capable of inducing chondrocytes and synovial cells to synthesize MMPs Furthermore; IL-1 suppresses the synthesis of type II collagen and proteoglycan. The original members of the IL-1 superfamily are IL-1α, IL-1β, and the IL-1 Receptor antagonist (IL-1RA). IL-1α and -β are pro-inflammatory cytokines involved in immune defense against infection. The IL-1RA is a molecule that competes for receptor binding with IL-1α and IL-1β, blocking their role in immune activation. Two forms of IL-1 bind to the same cellular receptor. This receptor is composed of two related, but non-identical, subunits that transmit intracellular signals via a pathway that is mostly shared with certain other receptors. IL-1α is a pleiotropic cytokine involved in various immune responses, inflammatory processes, and hematopoiesis.

Conclusion: If the receptors to which IL-1 alpha binds and becomes functional are blocked by putting some ligand over it, the degradation of cartilage can be stopped as the over expression of IL-1 alpha is prevented. There by we can put an end to the painful disease of osteoarthritis by which many people are loosing their active lives.


An article by Prathyusha Gopireddy (Btech Bioinformatics, SRM University, India) submitted on September 9, 2008 for Biology-Online.org.

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