Redox-Dependent Regulation of Interleukin-8 by Tumor Necrosis Factor-Alpha in Lung Epithelial Cells

Details

• Personal Author:
  Flood L ; Leonard, Stephanie ; Luster MI ; Simeonova PP ; Xianglin S
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Asbestos Asthma Asthma, Occupational Fibrosis Inorganic Chemicals Lung Lung Diseases Neoplasms Occupational Health Respiratory System Respiratory Tract Diseases Safety

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• Keywords:
  Asbestosis Bronchial-asthma Lung-cancer Neutrophils Pulmonary-disorders Respiratory-system-disorders Silicosis
• ISSN:
  0023-6837
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  79
• Issue:
  8
• NIOSHTIC Number:
  nn:20000969
• Citation:
  Lab Invest 1999 Aug; 79(8):1027-1037
• Email:
  phs9@cdc.gov
• Federal Fiscal Year:
  1999
• NORA Priority Area:
  Research Tools and Approaches: Cancer Research Methods
• Peer Reviewed:
  True
• Source Full Name:
  Laboratory Investigation
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:308ce9e149ffc0781830dfba336ed3a0dcb441974ffd9973cfc42d4afed45421f2aadf8b4ba9f0562ab594d66e78bf7592aeaab314bce9b6bb95204e4bb5bc9a
• Download URL:
  https://stacks.cdc.gov/view/cdc/198281/cdc_198281_DS1.pdf
• File Type:
  [PDF - 519.67 KB ]