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

Department of Pediatrics, Strong Children's Research Center, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642 Submitted 28 October 2002 ; accepted in final form 28 July 2003 The alveolar macrophage is an important source of interleukin (IL)-8 during pulmonary...

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Bibliographic Details
Published in:American journal of physiology. Lung cellular and molecular physiology 2004-01, Vol.286 (1), p.30
Main Authors: D'Angio, Carl T, LoMonaco, Michael B, Johnston, Carl J, Reed, Christina K, Finkelstein, Jacob N
Format: Article
Language:English
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Summary:Department of Pediatrics, Strong Children's Research Center, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642 Submitted 28 October 2002 ; accepted in final form 28 July 2003 The alveolar macrophage is an important source of interleukin (IL)-8 during pulmonary injury. The IL-8 gene promoter sequence contains nuclear factor (NF)- 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% CO 2 or 95% O 2 -5% CO 2 , with or without 1.0 µg/ml of LPS, and transfected with an IL-8 promoter-reporter containing NF- 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- B mutation ablated baseline and O 2 - 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- B in both cell lines. Pharmacological blockade of NF- B nuclear translocation ablated LPS-, but not hyperoxia-, stimulated IL-8 production. Although an intact promoter NF- B site is crucial to macrophage IL-8 production, only LPS-stimulated production appears to require additional nuclear translocation of NF- B. hyperoxia; U-937 cells; THP-1 cells; gene regulation; monocyte Address for reprint requests and other correspondence: C. T. D'Angio, Neonatology, Box 651, Golisano Children's Hospital at Strong, 601 Elmwood Ave., Rochester, NY 14642 (E-mail: carl_dangio{at}urmc.rochester.edu ).
ISSN:1040-0605
1522-1504
DOI:10.1152/ajplung.00360.2002