Modulation of NF-KappaB and Cytokine Responses in Lung Cells by Pro-Oxidant and Antioxidant Agents

Details

• Personal Author:
  Cosma G ; Gardner H ; Martinezv A ; Ufferfilge D ; Vallyathan V
• Description:
  Previous studies from our laboratory have indicated a central role for oxygen free radicals in lung pathogenesis following exposures to particulates. Current studies are investigating the modulation of DNA binding of transcription factor NF-kappaB by pro-oxidant and antioxidant agents, and the activities of proinftammatory cytokines interleukin-1/6, and TNF-alpha. Stimulation of rat alveolar macrophage NR8383 and human monocytic THP-l cell lines with organic particulates resulted in a ten-fold increase in NF-kappaB activity, as determined by electrophoretic mobility shift assay, by 45 min post-treatment which coincided with the production of hydrogen peroxide. IL-l and TNF-alpha levels, as detected by ELISA, increased by 6 hr, and IL-6 levels rose by 24 hr. Pre-treatments of cells with 20 mM n-acetylcysteine, previously shown to significantly inhibit hydrogen peroxide fomtation and cytokinc production in macrophages, did not result in inhibition of NF-kappaB activity in stimulated THP-I cells. The pineal hormone melatonin also did not appear to modulate DNA binding of NF-kappaB protein, despite a modest inhibition of hydrogen peroxide formation in cells. Interestingly, melatonin treated cells displayed a biphasic dose-response of synthesis of pro-inflammatory cytokines. Ongoing studies are further investigating the effects of melatonin on transcription factor activities and stress protein responses in lung cells, and its relationship to quenching of reactive oxygen species as detected by electron spin resonance. [Description provided by NIOSH]
• Subjects:
  Antioxidants Free Radicals Lung Lung Diseases Occupational Health Particulate Matter Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Antioxidation Free-radical-generation Free-radicals Lung-burden Lung-disease Lung-function Lung-irritants Lung-tissue Particulate-sampling-methods Particulates
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 10 ; OSHA Region 3 ; Washington ; 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:
  42
• NIOSHTIC Number:
  nn:20025107
• Citation:
  Toxicologist 1998 Mar; 42(1-S):346
• Federal Fiscal Year:
  1998
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 37th Annual Meeting, March 1-5,1998, Seattle, Washington
• Supplement:
  1-S
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:82c3c088f11836543339928885f4823b6f6371eff06bc401ef4488724923b4daaa1bead9814746d02c3ba9653b36781e7b6a32f1ecc567e1bb3315befd617d8b
• Download URL:
  https://stacks.cdc.gov/view/cdc/196603/cdc_196603_DS1.pdf
• File Type:
  [PDF - 132.76 KB ]