Nuclear Factor-Kappa Beta (NF-KB) Activity in Rat Alveolar Macrophages Exposed to Respirable Organic Particles and Antioxidants

Details

• Personal Author:
  Cosma GN ; Gardner H ; Ufferfilge D ; Vallyathan V
• Description:
  Activation of the transcription factor NF-kB by respirable organic particles (ROP) facilitates oxidative damage in lung through increased expression of pro-inflammatory genes. In previous studies, we found that NF-kB in alveolar macrophages was activated maximally at 2 hours following in vitro treatments with ROP. Because of the recent interest in identifying oxygen radical pathways of NF-kB activation, we have investigated inhibitory effects by specific antioxidant agents. NR8383 rat alveolar macrophage cells were treated with ROP, with and without antioxidants, and analyzed for NF-kB activation employing the electrophoretic mobility shift assay (EMSA). Densitometry analysis of EMSA gels revealed the following reductions in NF-KB activation (reported as % of positive control). 200 units/ml superoxide dismutase reduced activation by 51 %, whereas catalase had no inhibitory effect, strongly suggesting a primary role for the superoxide anion radical but not hydrogen peroxide, in the activation of NF-kB in alveolar macrophages. Furthermore, only a 270/0 reduction in NF-kB activation was observed following cell treatments with 1 nM melatonin, an efficient scavenger of hydrogen peroxide. A series of vitamin E species, alphatocopherol succinate, vitamin E acetate, and Trolox a vitamin E derivative, at 100 microM reduced NF-kB activation 63%, 33%, and 38%, respectively, clearly indicating that vitamin E analogs differ in their potencies of NF-kB inhibition. One microM pyrroHdinedithiocarbamate and 20 mM N-acetyl cysteine, which have effects on diverse oxygen free radical pathways, reduced NF-kB activation 54% and 66%, respectively, providing further support for a general role of reactive oxygen species in NF-kB activation. Ongoing studies are exploring the rote of lipopolysaccharide receptors and calcium regulatory pathways on NF-kB activation in lung cells following exposure to particulate matter. [Description provided by NIOSH]
• Subjects:
  Air Pollutants, Occupational Animals Antioxidants Chemistry Chemistry, Analytic Environmental Monitoring Hazardous Substances Laboratories Occupational Health Particulate Matter Safety Toxicology

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• Keywords:
  Airborne-particles Analytical-chemistry Analytical-methods Animal-studies Antioxidation Cell-transformation Cellular-reactions Exposure-assessment Laboratory-animals Particulate-dust Statistical-analysis Toxic-materials Toxins

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Colorado ; Louisiana ; Maryland ; OSHA Region 3 ; OSHA Region 6 ; OSHA Region 8 ; 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:
  48
• NIOSHTIC Number:
  nn:20027981
• Citation:
  Toxicologist 1999 Mar; 48(1-S):310
• CAS Registry Number:
  Tetrachloroethylene (CAS RN 127-18-4) ; Trichloroethylene (CAS RN 79-01-6)
• Federal Fiscal Year:
  1999
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 38th Annual Meeting, March 14-18, 1999, New Orleans, Louisiana
• Supplement:
  1-S
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:420857f4ec2a2ff2ea5402be573e7e708ccc52703011ca06c1bdf984f5a0a2c1ebb881397dfb36da6ccc41ceabaeb41166bdd4555789719945947d71c065d941
• Download URL:
  https://stacks.cdc.gov/view/cdc/189711/cdc_189711_DS1.pdf
• File Type:
  [PDF - 175.03 KB ]