Selective spleen tyrosine kinase inhibition delays autoimmune arthritis in mice

Zhang,Zuofu; Cao,Chunni; Sun,Shui; Xu,Qiang

doi:10.3892/mmr.2015.3759

Selective spleen tyrosine kinase inhibition delays autoimmune arthritis in mice

Authors:
- Zuofu Zhang
- Chunni Cao
- Shui Sun
- Qiang Xu
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Affiliations: Department of Joint Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, P.R. China, Department of Hyperbaric Oxygen, Yantai Yuhuangding Hospital, Yantai, Shandong 264000, P.R. China, Department of Joint Surgery, Yantai Yuhuangding Hospital, Yantai, Shandong 264000, P.R. China
Published online on: May 8, 2015 https://doi.org/10.3892/mmr.2015.3759
Pages: 2902-2906

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Abstract

Spleen tyrosine kinase (SYK) has an important role in immunoreceptor signaling, and SYK inhibition has accordingly attenuated immune‑mediated injury in several models. Therefore, the present study examined the effect of SYK inhibition with the selective spleen tyrosine kinase inhibitor P505‑15 in experimental rheumatoid arthritis (RA) using a murine model of collagen‑induced arthritis (CIA). Treatment with the selective SYK inhibitor P505‑15, a small molecule kinase inhibitor selective for SYK, led to a reduction in arthritis score and attenuated histological damage. P505‑15 reduced cartilage destruction and macrophage infiltration in CIA mice. In addition, P505‑15‑treated mice showed lower circulating levels of type II‑collagen immunoglobulin (Ig)G1 and IgG2 and pro‑inflammatory cytokines. Importantly, P505‑15 treatment markedly reduced the interleukin 1β‑stimulated 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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