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• W2038842078 endingPage "34" @default.
• W2038842078 startingPage "28" @default.
• W2038842078 abstract "Spleen tyrosine kinase (Syk) binds ITAM-bearing receptors in a wide variety of cell types. One such example is the activation of mast cells, basophils and eosinophils via the stimulation of the FcεRI receptor by IgE/allergen complexes. The possible role of Syk in inflammatory signaling cascades has led to the development of pharmacological agents designed to block the Syk catalytic domain as potential novel therapeutics. Whilst the enzymatic activity of Syk lends towards the design of small-molecule inhibitors, other attention has focused on the possibility of targeting Syk expression using anti-sense oligonucleotides as an alternate means of anti-inflammatory therapy. In this study, we compared the ability of multiple optimized Syk siRNA sequences and small-molecule Syk inhibitors to block FcεRI-mediated signal transduction, degranulation and TNFα secretion in the basophilic cell line RBL-2H3. We also characterized the specificity of each siRNA sequence with regards to off-target induction of the interferon-inducible gene IFIT1. We identified a single siRNA sequence, which displayed a favorable profile of efficient Syk knockdown, blockage of FcεRI-mediated signal transduction, degranulation and TNFα secretion and a lack of IFIT1 induction. The effect of this siRNA was comparable to that of the Syk kinase domain inhibitors BAY61-3606 and R406. The identification of an active and specific Syk siRNA could be a basis for the development of therapeutic Syk siRNAs against inflammatory diseases." @default.
• W2038842078 created "2016-06-24" @default.
• W2038842078 creator A5000011993 @default.
• W2038842078 creator A5006811358 @default.
• W2038842078 creator A5013156992 @default.
• W2038842078 creator A5018334465 @default.
• W2038842078 date "2010-01-01" @default.
• W2038842078 modified "2023-09-26" @default.
• W2038842078 title "Comparison of the anti-allergic activity of Syk inhibitors with optimized Syk siRNAs in FcεRI-activated RBL-2H3 basophilic cells" @default.
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• W2038842078 doi "https://doi.org/10.1016/j.cellimm.2009.12.004" @default.
• W2038842078 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7124319" @default.
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• W2038842078 hasPublicationYear "2010" @default.
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