Molecular mechanism of interleukin-8 gene expression.
A potent leukocyte chemotactic and activating cytokine, interleukin-8 (IL-8), is produced by numerous types of cells in response to inflammatory stimuli. Accumulating evidence indicate that the transcription of IL-8 gene requires the activation of either the combination of NF-kappa B and AP-1 or that of NF-kappa B and NF-IL6, depending on the type of cells. Alternatively, the activation of NF-kappa B is indispensable for IL-8 gene activation in any types of cells examined. On the other hand, an immunosuppressant, FK506, and a glucocorticoid inhibit the gene transcription as well as the production of IL-8. Molecular analyses of IL-8 gene repression by these agents revealed that both affected the activity of the transcription factor(s) bound to the NF-kappa B site, albeit in different ways, thereby suppressing IL-8 gene transcription. Collectively, IL-8 production seems to be controlled mainly at the activation step of the transcription factor(s) bound to the NF-kappa B site.
Mukaida
N
N
Department of Pharmacology, Kanazawa University, Ishikawa, Japan.
Okamoto
S
S
Ishikawa
Y
Y
Matsushima
K
K
D022762:CCAAT-Enhancer-Binding Proteins; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004586:Electrophoresis; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D016559:Tacrolimus / Q000494:pharmacology; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D007375:Interleukin-1; D016209:Interleukin-8; D016328:NF-kappa B; D009687:Nuclear Proteins; D012333:RNA, Messenger; D003907:Dexamethasone; D015500:Chloramphenicol O-Acetyltransferase; D016559:Tacrolimus