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• W3085050545 abstract "The impact of spleen tyrosine kinase (Syk) signaling might be prominent in lupus because (i) Syk is a shared downstream signaling molecule among circulating immune complex, LPS, and (1→3)-β-D-glucan (BG), and (ii) all of these factors are detectable in the serum of Fc gamma receptor IIb-deficient (FcgRIIb^−/−) mice with sepsis. As a proof of concept study, we activated macrophages with BG combined with LPS (BG + LPS). We found that BG + LPS predominantly upregulated Syk expression and proinflammatory cytokines in FcgRIIb^−/− macrophages compared with wild-type (WT) macrophages. Syk inhibition downregulated several inflammatory pathways in FcgRIIb^−/− macrophages activated with BG + LPS, as determined by RNA sequencing analysis, suggesting the potential anti-inflammatory impact of Syk inhibitors in lupus. Indeed, administration of a Syk inhibitor prior to cecal ligation and puncture (CLP) sepsis in FcgRIIb^−/− mice reduced baseline lupus-induced proinflammatory cytokines and attenuated sepsis severity as evaluated by mortality, organ injury, serum LPS, and post-sepsis serum cytokines. In conclusion, it was easier to induce Syk expression in FcgRIIb^−/− macrophages than in WT macrophages. This might be because of the loss of inhibitory signaling, which might be responsible for prominent Syk abundance in the spleens of 40-week-old FcgRIIb^−/− mice and the potent effect of Syk inhibitor in lupus mice compared with WT." @default.
• W3085050545 created "2020-09-21" @default.
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• W3085050545 date "2020-01-01" @default.
• W3085050545 modified "2023-10-14" @default.
• W3085050545 title "Syk Inhibitor Attenuates Polymicrobial Sepsis in FcgRIIb-Deficient Lupus Mouse Model, the Impact of Lupus Characteristics in Sepsis" @default.
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• W3085050545 doi "https://doi.org/10.1159/000509111" @default.
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