Lipopolysaccharide-induced Tumor Necrosis Factor-α Promoter Activity Is Inhibitor of Nuclear Factor-κB Kinase-dependent
The adverse effects of lipopolysaccharide (LPS) are primarily mediated by tumor necrosis factor-α (TNF-α). TNF-α production by LPS-stimulated macrophages is regulated both transcriptionally and post-transcriptionally. Transcriptional regulation of the TNF-α gene is dependent on nuclear factor-κ...
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Published in | The Journal of biological chemistry Vol. 274; no. 17; p. 11667 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
American Society for Biochemistry and Molecular Biology
23.04.1999
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Online Access | Get full text |
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Summary: | The adverse effects of lipopolysaccharide (LPS) are primarily mediated by tumor necrosis factor-α (TNF-α). TNF-α production
by LPS-stimulated macrophages is regulated both transcriptionally and post-transcriptionally. Transcriptional regulation of
the TNF-α gene is dependent on nuclear factor-κB (NF-κB). We examined the signaling pathways involved in the regulation of
NF-κB that lead to TNF-α promoter activity. We determined a role for one or both of the recently identified inhibitor of NF-κB
kinases, IκB kinase-1 and IκB kinase-2, in LPS induction of an NF-κB reporter and of TNF-α promoter activity. IκB kinase activation
is one of the earliest signaling events known to be induced by LPS. Furthermore, our results suggest roles for the IκB kinases
NF-κB-inducing kinase and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 1 in the regulation
of IκB kinase-2, as well as in LPS-induced TNF-α transcription. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.274.17.11667 |