Regulation of COX-2 Expression and IL-6 Release by Particulate Matter in Airway Epithelial Cells

Details

• Personal Author:
  Breysse PN ; Garcia JGN ; Geyh AS ; Gorshkova IA ; He D ; Moreno-Vinasco L ; Natarajan V ; Samet JM ; Spannhake EW ; Usatyuk PV ; Wang T ; Zhao Y ; Breysse PN ; Garcia JGN ; Geyh AS ; Gorshkova IA ; He D ; Moreno-Vinasco L ; Natarajan V ; Samet JM ; Spannhake EW ; Usatyuk PV ; Wang T ; Zhao Y
• Description:
  Particulate matter (PM) in ambient air is a risk factor for human respiratory and cardiovascular diseases. The delivery of PM to airway epithelial cells has been linked to release of proinflammatory cytokines; however, the mechanisms of PM-induced inflammatory responses are not well-characterized. This study demonstrates that PM induces cyclooxygenase (COX)-2 expression and IL-6 release through both a reactive oxygen species (ROS)-dependent NF-kappaB pathway and an ROS-independent C/EBPbeta pathway in human bronchial epithelial cells (HBEpCs) in culture. Treatment of HBEpCs with Baltimore PM induced ROS production, COX-2 expression, and IL-6 release. Pretreatment with N-acetylcysteine (NAC) or EUK-134, in a dose-dependent manner, attenuated PM-induced ROS production, COX-2 expression, and IL-6 release. The PM-induced ROS was significantly of mitochondrial origin, as evidenced by increased oxidation of the mitochondrially targeted hydroethidine to hydroxyethidium by reaction with superoxide. Exposure of HBEpCs to PM stimulated phosphorylation of NF-kappaB and C/EBPbeta, while the NF-kappaB inhibitor, Bay11-7082, or C/EBPbeta siRNA attenuated PM-induced COX-2 expression and IL-6 release. Furthermore, NAC or EUK-134 attenuated PM-induced activation of NF-kappaB; however, NAC or EUK-134 had no effect on phosphorylation of C/EBPbeta. In addition, inhibition of COX-2 partly attenuated PM-induced Prostaglandin E2 and IL-6 release. [Description provided by NIOSH]
• Subjects:
  Air Pollutants, Occupational Air Pollution Immune System Occupational Health Particulate Matter Respiratory System Safety
• Keywords:
  Airborne Particles Air Pollution Airway Epithelium Author Keywords: Ambient Particulate Matter Cytokine Cytokines Immune Reaction Particulates Physiological Effects Reactive Oxygen Species Respiratory Irritants ROS Transcriptional Factors

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• ISSN:
  1044-1549
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article ; Journal Article
• Place as Subject:
  Illinois ; Maryland ; OSHA Region 3 ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH) ; National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health ; Workplace Safety & Health
• Location:
  North America ; North America
• Pages in Document:
  19-30
• Volume:
  40
• Issue:
  1
• NIOSHTIC Number:
  nn:20062771
• Citation:
  Am J Respir Cell Mol Biol 2009 Jan; 40(1):19-30
• Contact Point Address:
  Viswanathan Natarajan, Ph.D., Section of Pulmonary and Critical Care, Department of Medicine, Center for Integrative Science Building, Room W408B, 929 East 57th Street, Chicago, IL 60637
• Email:
  vnataraj@medicine.bsd.uchicago.edu
• Federal Fiscal Year:
  2009
• Performing Organization:
  Johns Hopkins University
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  American Journal of Respiratory Cell and Molecular Biology
• End Date:
  20280630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:9b6a9bb58dd5c71b83712c639f16262cd2a0f8d8e0650b6bf2e279a1173ec4f3c6caa5f06f11292c9845a7c8135673170731db58d3d73969c9b23ad101654e18
• Download URL:
  https://stacks.cdc.gov/view/cdc/225961/cdc_225961_DS1.pdf
• File Type:
  [PDF - 1.31 MB ]