Session Type: Abstract Submissions (ACR)
Background/Purpose The possible antifibrotic effects of various kinase inhibitors has been studied before in SSc. Spleen tyrosine kinase (Syk) is a protein tyrosine kinase which activates intracellular signal transduction pathways and has been claimed to be involved in the pathogenesis of systemic autoimmune diseases. We investigated the ability of a small drug Syk inhibitor, fostamatinib, to protect mice from bleomycin-induced SSc.
Methods Four study groups of Balb/c mice were included in this study: control, bleomycin (administered subcutaneously to BALB/c mice for 21 days), bleomycin and fostamatinib (mice fed with chow containing a Syk inhibitor for 21 days) and fostamatinib alone groups. Skin and lung tissue specimens were obtained and evaluated histologically.
Results Mice treated with bleomycin alone had significantly more skin thickness (416.1±6.1) compared to control (260.1±10.1) and fostamatinib (254.3±7.9) treated mice (p<0.001). Mice subjected to bleomycin and fed with fostamatinib-containing chow generated more (312.3±4.4) dermal thickness than control and fostamatinib-treated mice (p values <0.001) but, significantly less when compared to mice treated with bleomycin alone (p<0.001).Alveolar hemorrhage, edema, damage and leukocyte scores in the lungs of mice treated with bleomycin were significantly higher v compared to control or fostamatinib alone-treated mice (p values <0.001). At the end of the 21-day bleomycin administration, there was apparent prominent fibrosis which was reduced significantly in the group of mice which received in parallel fostamatinib. Following fostamatinib treatment, Syk, phospho-Syk, and TGF-β expression decreased in both skin and lung tissues
Conclusion The Syk inhibitor fostamatinib prevented bleomycin-induced fibrosis and inflammation in the skin and the lung. The anti-fibrotic effect of fostamatinib is linked to reduced Syk phosphorylation and TGF-β expression. The Syk pathway appears as a potential molecular target for therapeutic intervention in SSc.
O. N. Pamuk,
G. C. Tsokos,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-syk-inhibitor-fostamatinib-limits-tissue-damage-and-fibrosis-in-a-bleomycin-induced-scleroderma-mouse-model/