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Öğe Spleen tyrosine kinase inhibition in the treatment of autoimmune, allergic and autoinflammatory diseases(Bmc, 2010) Pamuk, Omer N.; Tsokos, George C.Spleen tyrosine kinase (Syk) is involved in the development of the adaptive immune system and has been recognized as being important in the function of additional cell types, including platelets, phagocytes, fibroblasts, and osteoclasts, and in the generation of the inflammasome. Preclinical studies presented compelling evidence that Syk inhibition may have therapeutic value in the treatment of rheumatoid arthritis and other forms of arthritis, systemic lupus erythematosus, autoimmune cytopenias, and allergic and autoinflammatory diseases. In addition, Syk inhibition may have a place in limiting tissue injury associated with organ transplant and revascularization procedures. Clinical trials have documented exciting success in the treatment of patients with rheumatoid arthritis, autoimmune cytopenias, and allergic rhinitis. While the extent and severity of side effects appear to be limited so far, larger studies will unravel the risk involved with the clinical benefit.Öğe SPLEEN TYROSINE KINASE INHIBITION PREVENTS TISSUE DAMAGE AFTER ISCHAEMIA REPERFUSION INJURY(Oxford Univ Press, 2011) Pamuk, Omer Nuri; Lapchak, Peter H.; Rani, Poonam; Pine, Polly; Dalle Luca, Jurandir J.; Tsokos, George C.[Abstract Not Available]Öğe Spleen tyrosine kinase inhibition prevents tissue damage after ischemia-reperfusion(Amer Physiological Soc, 2010) Pamuk, Omer Nuri; Lapchak, Peter H.; Rani, Poonam; Pine, Polly; Lucca, Jurandir J. Dalle; Tsokos, George C.Pamuk ON, Lapchak PH, Rani P, Pine P, Dalle Lucca JJ, Tsokos GC. Spleen tyrosine kinase inhibition prevents tissue damage after ischemia-reperfusion. Am J Physiol Gastrointest Liver Physiol 299: G391-G399, 2010. First published June 3, 2010; doi: 10.1152/ajpgi.00198.2010.-Reperfusion injury to tissue following an ischemic event occurs as a consequence of an acute inflammatory response that can cause significant morbidity and mortality. Components of both the innate (complement, immunoglobulin, monocytes, and neutrophils) and adaptive (B and T lymphocytes) immune systems have been demonstrated to mediate tissue injury. Spleen tyrosine kinase (Syk) is responsible for membrane-mediated signaling in various cell types including B lymphocytes, macrophages, and T cells. We investigated the ability of a small drug Syk inhibitor, R788, to protect mice against mesenteric ischemia-reperfusion (I/R)-induced local (intestine) and remote lung injury. Mice were fed with chow containing a Syk inhibitor for 6 days before the performance of intestinal I/R, which resulted in silencing of the expression of the active phosphorylated Syk. Syk inhibition significantly suppressed both local and remote lung injury. The beneficial effect was associated with reduced IgM and complement 3 deposition in the tissues and significant reduction of polymorphonuclear cell infiltration. Our data place Syk upstream of events leading to the binding of natural antibodies to the ischemia-conditioned tissues and urge the consideration of the use of Syk inhibitors in the prevention or improvement of tissue injury of organs exposed to ischemia or hypoperfusion.Öğe The SYK Inhibitor Fostamatinib Limits Tissue Damage and Fibrosis in a Bleomycin-Induced Scleroderma MOUSE MODEL(Wiley, 2014) Pamuk, Omer Nuri; Can, Guray; Ayvaz, Suleyman; Karaca, Turan; Pamuk, Gulsum; Demirtas, Selim; Tsokos, George C.[Abstract Not Available]
