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• W3038862610 startingPage "173340" @default.
• W3038862610 abstract "Sepsis is a serious condition that can lead to long-term organ damage and death. At the molecular level, the hallmark of sepsis is the elevated expression of a multitude of potent cytokines, i.e. a cytokine storm. For sepsis involving gram-negative bacteria, macrophages recognize lipopolysaccharide (LPS) shed from the bacteria, activating Toll-like-receptor 4 (TLR4), and triggering a cytokine storm. Glycogen synthase kinase-3 (GSK-3) is a highly active kinase that has been implicated in LPS-induced cytokine production. Thus, compounds that inhibit GSK-3 could be potential therapeutics for sepsis. Our group has recently described a novel and highly selective inhibitor of GSK-3 termed COB-187. In the present study, using THP-1 macrophages, we evaluated the ability of COB-187 to attenuate LPS-induced cytokine production. We found that COB-187 significantly reduced, at the protein and mRNA levels, cytokines induced by LPS (e.g. IL-6, TNF-α, IL-1β, CXCL10, and IFN-β). Further, the data suggest that the inhibition could be due, at least in part, to COB-187 reducing NF-κB (p65/p50) DNA binding activity as well as reducing IRF-3 phosphorylation at Serine 396. Thus, COB-187 appears to be a potent inhibitor of the cytokine storm induced by LPS." @default.
• W3038862610 created "2020-07-10" @default.
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• W3038862610 date "2020-09-01" @default.
• W3038862610 modified "2023-10-18" @default.
• W3038862610 title "Modulation of LPS-induced inflammatory cytokine production by a novel glycogen synthase kinase-3 inhibitor" @default.
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• W3038862610 doi "https://doi.org/10.1016/j.ejphar.2020.173340" @default.
• W3038862610 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7334664" @default.
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