Superinduction of NF-kappa B by actinomycin D and cycloheximide in epithelial cells.
Epithelial cells are actively involved in inflammation and play a role in inflammatory diseases such as asthma. Numerous proinflammatory genes, expressed in the airway epithelium, are regulated by the transcription factor NF-kappa B. We show that the proinflammatory cytokines, IL-1 beta and TNF alpha, as well as a protein kinase C activator cause NF-kappa B activation in A549 epithelial cells. This observation is consistent with a major role for NF-kappa B in inflammation. We also demonstrate that IL-1 beta costimulation with a protein synthesis inhibitor, cycloheximide, or a transcription blocker, actinomycin D, results in superinduction of NF-kappa B but not the transcription factors Oct 1, AP-1, and Sp-1. We speculate that this may be due to lack of de novo synthesis of the NF-kappa B inhibitor, I kappa B alpha, and suggest that this phenomena may help explain the widely observed effect of mRNA superinduction of primary response genes in response to translational blockers.
Newton
R
R
Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, London, UK.
Adcock
I M
IM
Barnes
P J
PJ
D001483:Base Sequence; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D018398:Homeodomain Proteins / Q000378:metabolism; D051863:Host Cell Factor C1; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000235:genetics; D050811:Octamer Transcription Factor-1; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011493:Protein Kinase C / Q000502:physiology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D016329:Sp1 Transcription Factor / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D004268:DNA-Binding Proteins; C497692:HCFC1 protein, human; D018398:Homeodomain Proteins; D051863:Host Cell Factor C1; D007375:Interleukin-1; D016328:NF-kappa B; D050811:Octamer Transcription Factor-1; D009838:Oligodeoxyribonucleotides; C494165:POU2F1 protein, human; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D016329:Sp1 Transcription Factor; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D003513:Cycloheximide; D019001:Nitric Oxide Synthase; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate