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• W2134237689 abstract "Nuclear factor (NF)-κB activation is a critical step in the triggering of inflammatory responses by macrophages. Although numerous investigations have been reported, the precise regulatory mechanisms controlling inflammatory responses mediated by NF-κB remain unclear. In this study, we investigated the early signaling events responsible for modulating NF-κB activation using various parameters, such as the expression of pro-inflammatory genes and the phosphorylation levels of inhibitor of κBα (IκBα) and its upstream kinases. Lipopolysaccharide (LPS) treatment biphasically induced activation of IκBα phosphorylation at 5 and 30 min, which induced subsequent pro-inflammatory gene expression that was maximized at 45 and 90 min. Of the intracellular signals tested, a series of signaling cascades composed of spleen tyrosine kinase (Syk), phosphoinositide-3-kinase (PI3K), and Akt (protein kinase B) were involved in regulating early phosphorylation of IκBα, according to biochemical and pharmacological analyses. Therefore, our data suggests that Syk-mediated activation of intracellular signaling in response to LPS may play an important role in LPS-induced inflammatory signaling events. Thus, Syk may be a potential target for the development of potent anti-inflammatory drugs." @default.
• W2134237689 created "2016-06-24" @default.
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• W2134237689 date "2009-04-01" @default.
• W2134237689 modified "2023-09-27" @default.
• W2134237689 title "Distinct role of spleen tyrosine kinase in the early phosphorylation of inhibitor of κBα via activation of the phosphoinositide-3-kinase and Akt pathways" @default.
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• W2134237689 doi "https://doi.org/10.1016/j.biocel.2008.08.011" @default.
• W2134237689 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18775507" @default.
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