Oxidant-mediated increases in redox factor-1 nuclear protein and activator protein-1 DNA binding in asbestos-treated macrophages

Dawn M Flaherty; Martha M Monick; A Brent Carter; Michael W Peterson; Gary W Hunninghake

doi:10.4049/jimmunol.168.11.5675

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Oxidant-mediated increases in redox factor-1 nuclear protein and activator protein-1 DNA binding in asbestos-treated macrophages

Journal article

Peer reviewed

Oxidant-mediated increases in redox factor-1 nuclear protein and activator protein-1 DNA binding in asbestos-treated macrophages

Dawn M Flaherty, Martha M Monick, A Brent Carter, Michael W Peterson and Gary W Hunninghake

The Journal of immunology (1950), Vol.168(11), pp.5675-5681

06/01/2002

DOI: 10.4049/jimmunol.168.11.5675

PMID: 12023366

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Abstract

Alveolar macrophages have been implicated in the pathogenesis of a number of acute and chronic lung disorders. We have previously shown that normal human alveolar macrophages exhibit decreased DNA binding activity of the transcription factor, AP-1, compared with monocytes. Furthermore, this decrease in AP-1 DNA binding appears to be due to a decrease in the redox active protein, redox factor (Ref)-1. Ref-1 is an important redox regulator of a number of transcription factors, including NF-kappaB and AP-1. In this study we evaluated the role of asbestos, a prototypic model of chronic fibrotic lung disease, in Ref-1 expression and activity. We found that incubation with low concentrations of crocidolite asbestos (0.5-1.25 microg/cm(2)) resulted in an increase in nuclear Ref-1 protein after 5 min, with a persistent elevation in protein up to 24 h. Additionally, an increase in nuclear Ref-1 could be induced by treating the cells with an oxidant-generating stimulus (iron loading plus PMA) and inhibited by diphenyleneiodonium chloride, an inhibitor of NADPH oxidase. The asbestos-induced accumulation of nuclear Ref-1 was associated with an increase in AP-1 DNA binding activity. These findings suggest that an exposure associated with fibrotic lung disease, i.e., asbestos, modulates accumulation of nuclear Ref-1 in macrophages, and that this effect is mediated by an oxidant stimulus.

Cell Line

Reactive Oxygen Species

Carbon-Oxygen Lyases - biosynthesis

Humans

NADPH Oxidases - antagonists & inhibitors

DNA - metabolism

Transcription Factor AP-1 - metabolism

Asbestos, Crocidolite - toxicity

Animals

DNA-(Apurinic or Apyrimidinic Site) Lyase

Macrophages, Alveolar - drug effects

Mice

Macrophages, Alveolar - metabolism

Iron - pharmacology

Details

Title: Subtitle: Oxidant-mediated increases in redox factor-1 nuclear protein and activator protein-1 DNA binding in asbestos-treated macrophages
Creators: Dawn M Flaherty - Department of Internal Medicine, University of Iowa College of Medicine and Veterans Affairs Medical Center, Iowa City, IA 52243, USA. flahertydm@mail.medicine.uiowa.edu
Martha M Monick
A Brent Carter
Michael W Peterson
Gary W Hunninghake
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.168(11), pp.5675-5681
DOI: 10.4049/jimmunol.168.11.5675
PMID: 12023366
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Grant note: HL60316 / NHLBI NIH HHS
Language: English
Date published: 06/01/2002
Academic Unit: Pulmonary, Critical Care, and Occupational Medicine; Radiation Oncology; Internal Medicine
Record Identifier: 9984094602502771

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