| Two different tumor necrosis factors,first isolated in 1984,were found to induce tumor regression in mice.Research during the past three decades has shown the existence of a superfamily of TNF proteins consisting of 19 members that signal through 29 receptors.These ligands,while regulating normal functions such as hematopoiesis,morphogenesis and immune responses,have also been related with transplant rejection,septic,shock,bone resorption,tumorigenesis,diabetes,viral replication and rheumatoid arthritis.These cytokines either induce cellular survival,differentiation,proliferation,or apoptosis.Blockers of TNF have been approved for human use in treating TNF-linked autoimmune diseases in many countries.TNF-a is well known to act in inflammatory reaction of some autoimmune diseases,such as inflammatory bowel disease and rheumatoid arthritis.When this cytokine is produced in large scale,such as in severe infection,it may induce shock or decrease of blood pressure due to reducing vascular muscle tone and myocardial contractility,in addition,high concentrations TNF can reduce blood glucose concentration,and cause intravascular thrombosis.Under these conditions,the treatment of these diseases can be through compound targeting TNF.In this study,we constructed the expression vector of TNF-a by molecular biology technologies and obtained TNF-a crystal to a resolution of 3 A.We aim to find some small molecular compounds that can interact with TNF-a protein,laying a foundation for the development of drugs for TNF-related diseases. |
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