Abstract: Matrix metalloproteinases are major mediators of tissue destruction in various chronic inflammatory disorders. The present invention demonstrates that over-expression of intracellular isoform of IL-1 receptor antagonist confers to recipient cells resistance to signaling pathways of proinflammatory cytokines (such as tumor necrosis factor alpha and IL-1 beta) that induce matrix metalloproteinase and subsequent tissue degradation. Hence, over-expression of intracellular IL-1 receptor antagonist may inhibit tissue destruction in various inflammatory disorders such as rheumatoid arthritis, other arthritides, degenerative intervertebral disc disease and chronic skin ulcers that occurs in diabetes mellitus and bed-ridden patients.

Abstract: The present invention has demonstrated for the first time that orally administered type I collagen (CI) induced tolerance to CI in patients suffering from systemic sclerosis (SSc) and ameliorated clinical manifestations of the disease. Accordingly, the present invention provides methods of treating a fibrosing disease by oral administration of a tissue protein, for example, collagen, derived from the tissue undergoing fibrosis.

Abstract: Matrix metalloproteinases are major mediators of tissue destruction in various chronic inflammatory disorders. The present invention demonstrates that over-expression of intracellular isoform of IL-1 receptor antagonist confers to recipient cells resistance to signaling pathways of proinflammatory cytokines (such as tumor necrosis factor alpha and IL-1 beta) that induce matrix metalloproteinase and subsequent tissue degradation. Hence, over-expression of intracellular IL-1 receptor antagonist may inhibit tissue destruction in various inflammatory disorders such as rheumatoid arthritis, other arthritides, degenerative intervertebral disc disease and chronic skin ulcers that occurs in diabetes mellitus and bed-ridden patients.