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Redox-dependent regulation of interleukin-8 by tumor necrosis factor-alpha in lung epithelial cells.

Authors
Simeonova-PP; Leonard-S; Flood-L; Xianglin-S; Luster-MI
Source
Lab Invest 1999 Aug; 79(8):1027-1037
NIOSHTIC No.
20000969
Abstract
Increasing evidence supports a major role for interleukin-8 (IL-8), a potent neutrophil chemoattractant, in the chronic progression of inflammatory lung diseases. The present studies were designed to characterize the molecular events involved in IL-8 induction in pulmonary epithelial cells in response to tumor necrosis factor-alpha (TNF-alpha). IL-8 induction by TNF-alpha was redox sensitive, as indicated by electron spin resonance analysis and inhibition with membrane permeable hydroxyl scavengers. Furthermore using cell transfection and mobility shift assays, it was found that transcriptional activation of the IL-8 gene required TNF-alpha-induced activation and binding of nuclear factor-kappaB (NF-kappaB)- and NF-IL-6, nuclear transcription factors to regulatory elements in the IL-8 promoter. Activation of the IL-8 promoter by these transcription factors was also redox-sensitive. This response was mediated through the TNF-R1 receptor (p55), and not the TNF-R2 (p75) receptor, although both receptors can be found on pulmonary epithelial cells. Taken together these studies indicate that TNF-alpha-induced redox changes in lung epithelial cells are responsible for the transcriptional activation of IL-8 and that coordinate activation of NF-kappaB and NF-IL-6 mediate the response.
Keywords
Pulmonary-disorders; Fibrosis; Asbestosis; Neutrophils; Respiratory-system-disorders; Lung-cancer; Bronchial-asthma; Silicosis
CODEN
LAINAW
Publication Date
19990801
Document Type
Journal Article
Email Address
phs9@cdc.gov
Fiscal Year
1999
NTIS Accession No.
NTIS Price
Issue of Publication
8
ISSN
0023-6837
NIOSH Division
HELD
Priority Area
Research Tools and Approaches; Cancer Research Methods
Source Name
Laboratory Investigation
State
WV
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