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Selective spleen tyrosine kinase inhibition delays autoimmune arthritis in mice

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Spleen tyrosine kinase (SYK) has an important role in immunoreceptor signaling, and SYK inhibition has accordingly attenuated immunemediated injury in several models. Therefore, the present study examined the effect of SYK inhibition with the selective spleen tyrosine kinase inhibitor P50515 in experimental rheumatoid arthritis (RA) using a murine model of collageninduced arthritis (CIA). Treatment with the selective SYK inhibitor P50515, a small molecule kinase inhibitor selective for SYK, led to a reduction in arthritis score and attenuated histological damage. P50515 reduced cartilage destruction and macrophage infiltration in CIA mice. In addition, P50515treated mice showed lower circulating levels of type IIcollagen immunoglobulin (Ig)G1 and IgG2 and proinflammatory cytokines. Importantly, P50515 treatment markedly reduced the interleukin¬†1βstimulated inflammatory response in human RA synovial cells. Given these encouraging results, a key function for SYK in the development of RA was identified, highlighting that SYK may be a potential therapeutic target for human RA.
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Document Type: Research Article

Affiliations: 1: Department of Joint Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, P.R. China 2: Department of Hyperbaric Oxygen, Yantai Yuhuangding Hospital, Yantai, Shandong 264000, P.R. China 3: Department of Joint Surgery, Yantai Yuhuangding Hospital, Yantai, Shandong 264000, P.R. China

Publication date: August 1, 2015

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  • Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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