Differential roles for NF-kappa B in endotoxin and oxygen induction of interleukin-8 in the macrophage

The alveolar macrophage is an important source of interleukin (IL)-8 during pulmonary injury. The IL-8 gene promoter sequence contains nuclear factor (NF)-kappa B, NF-IL6, and activator protein (AP)-1 binding sequences. These sites may have differing regulatory roles in hyperoxia-exposed macrophages...

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Bibliographic Details
Published in:American journal of physiology. Lung cellular and molecular physiology 2004-01, Vol.286 (1), p.L30-L36
Main Authors: D'Angio, Carl T, LoMonaco, Michael B, Johnston, Carl J, Reed, Christina K, Finkelstein, Jacob N
Format: Article
Language:English
Subjects:
CCAAT-Enhancer-Binding Protein-beta - metabolism
Cell Nucleus - metabolism
Gene Expression Regulation - drug effects
Gene Expression Regulation - immunology
Humans
Hyperoxia - physiopathology
Interleukin-8 - genetics
Interleukin-8 - secretion
Lipopolysaccharides - pharmacology
Macrophages - drug effects
Macrophages - physiology
NF-kappa B - metabolism
Oxidative Stress - physiology
Oxygen - pharmacology
Promoter Regions, Genetic
RNA, Messenger - analysis
Transcription Factor AP-1 - metabolism
U937 Cells
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Summary:The alveolar macrophage is an important source of interleukin (IL)-8 during pulmonary injury. The IL-8 gene promoter sequence contains nuclear factor (NF)-kappa B, NF-IL6, and activator protein (AP)-1 binding sequences. These sites may have differing regulatory roles in hyperoxia-exposed macrophages than in those stimulated by bacterial lipopolysaccharide (LPS). U-937 and THP-1 macrophage-like cells were exposed to air-5% CO2 or 95% O2-5% CO2, with or without 1.0 microg/ml of LPS, and transfected with an IL-8 promoter-reporter containing NF-kappa B, NF-IL6, or AP-1 mutations. Hyperoxia and LPS caused additive increases in IL-8 production by U-937 cells, whereas THP-1 cells responded only to LPS. An NF-kappa B mutation ablated baseline and O2- and LPS-stimulated reporter activity in both cell lines, whereas NF-IL6 mutations had little effect. An AP-1 mutation had an intermediate effect. LPS, but not hyperoxia, stimulated nuclear translocation of NF-kappa B in both cell lines. Pharmacological blockade of NF-kappa B nuclear translocation ablated LPS-, but not hyperoxia-, stimulated IL-8 production. Although an intact promoter NF-kappa B site is crucial to macrophage IL-8 production, only LPS-stimulated production appears to require additional nuclear translocation of NF-kappa B.
ISSN:1040-0605
1522-1504
DOI:10.1152/ajplung.00360.2002