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. 2022 May 5;13:885053. doi: 10.3389/fphar.2022.885053

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Copyright © 2022 Liu, Hua, Bao, Kong, Hu, Liu, Li, Xu and Liu.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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The Syk inhibitor R406 ameliorates glucocorticoid resistance in steroid-resistant asthma. Syk is essential for regulating inflammatory signaling in steroid-resistant asthma. The Syk inhibitor R406 can reduce the phosphorylation of GR-Ser226 by inhibiting allergen- or TNF-α-induced MAPK phosphorylation and restore the nuclear translocation of GR. R406 promotes dexamethasone-mediated inhibition of n NF-κB, restores HDAC2 activity, increases the expression of the glucocorticoid-responsive element GILZ, and reduces the expression of cytokines such as IL-8 to improve sensitivity to glucocorticoids in severe asthma.