Novel Protein

About

Description Cytokines are a diversegroup of multifunctional proteins, secreted by white blood cells and a varietyof other cells in the body, which affect almost every aspect of immunity.Cytokines have been shown to function as: (1) mediators of natural immunity; (2)regulators of lymphocyte activation, growth and differentiation; (3) activatorsof nonspecific inflammatory cells; and (4) stimulators of hematopoiesis. Wellknown cytokines include the interferons, tumor necrosis factor, theinterleukins and the family of colony-stimulating factors (GM-CSF, M-CSF andG-CSF). There has been great interest in this group of molecules over the past40 years, especially as their seminal role in immune modulation has beenelucidated.   Description of the Project: Dr. Vilcek, a recognized world leader in cytokine research, recently discovereda new gene coding for a cytokine-related protein. The gene sequence wasinitially identified from cloned cDNAs obtained from human diploid FS-4fibroblasts stimulated with tumor necrosis factor (TNF). TSG-6 (TSG andTNF-stimulated gene) is a secreted 35KD hyaluronate binding protein that isstructurally related to cartilage link protein, proteoglycan core proteins andthe adhesion receptor CD44. TSG-6 is also induced by IL-1 and LPS. Functionally,TSG-6 appears to be involved in the inflammatory process. High levels of TSG-6have been demonstrated in the synovial fluids of a majority of arthritispatients. The anti-inflammatory role of TSG-6 has recently been demonstrated invivo in a murine acute inflammation model, where administration of TSG-6effectively blocked inflammatory response, comparable to systemic dexamethasonetreatment. TSG-6 forms a stable complex with components of the serine proteaseinhibitor, inter-a-inhibitor. The anti-inflammatory effect ofTNF/Il-1-inducible TSG-6 protein, along with its ability to inhibit proteaseaction through inter-a-inhibitor, suggests that TSG-6 is part of a negativefeedback loop operating through the protease network.   Applications: NYU is seeking an industrial partner to assist the development of this novelcytokine for human diagnostic and therapeutic applications.