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• W1936935448 endingPage "2134" @default.
• W1936935448 startingPage "2128" @default.
• W1936935448 abstract "Abstract Although the precise mechanisms by which steroids mediate their therapeutic effects remain unknown, steroids have been reported to abrogate cytokine-induced activation of the transcription factor NF-κB. In some cell types, NF-κB activation is necessary to regulate cytokine-mediated cellular functions. However, compelling evidence suggests that the steroid inhibition of NF-κB is complex and cell specific. Using EMSA, we show that stimulation with TNF-α or IL-1β induces NF-κB DNA-binding activity in human airway smooth muscle cells. TNF-α and IL-1β also increased luciferase activity in airway smooth muscle cells transfected with a reporter plasmid containing κB enhancer elements. Cytokines activated NF-κB by rapidly degrading its cytosolic inhibitor IκBα, which was then regenerated after 60 min. Cytokine-mediated IκBα reappearance was completely blocked by the protein synthesis inhibitor cycloheximide. Inhibition of cytokine-mediated IκBα proteolysis using the protease inhibitors N-tosyl-l-phenylalanine chloromethyl ketone and N-acetyl-l-leucinyl-l-leucinyl-norleucinal also inhibited cytokine-mediated early expression of ICAM-1. Although dexamethasone partially inhibited IL-1β- and TNF-α-induced up-regulation of ICAM-1 at 4 h, dexamethasone had no effect on cytokine-induced ICAM-1 expression at 18–24 h. In addition, neither cytokine-induced degradation or resynthesis of IκBα nor NF-κB DNA-binding activity were affected by dexamethasone. In cells transfected with the luciferase reporter, dexamethasone did not affect TNF-α-induced NF-κB-dependent transcription. Interestingly, cytokine-mediated expression of cyclooxygenase-2 was completely abrogated by dexamethasone at 6 h. Together, these data demonstrate that cytokine-mediated NF-κB activation and ICAM-1 expression involve activation of a steroid-insensitive pathway." @default.
• W1936935448 created "2016-06-24" @default.
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• W1936935448 creator A5079628483 @default.
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• W1936935448 date "1999-08-15" @default.
• W1936935448 modified "2023-10-17" @default.
• W1936935448 title "Up-Regulation of ICAM-1 by Cytokines in Human Tracheal Smooth Muscle Cells Involves an NF-κB-Dependent Signaling Pathway That Is Only Partially Sensitive to Dexamethasone" @default.
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• W1936935448 doi "https://doi.org/10.4049/jimmunol.163.4.2128" @default.
• W1936935448 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/10438953" @default.
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