title: Linking oxidative events to inflammatory and adaptive gene expression induced by exposure to an organic particulate matter component.
abstract: BACKGROUND
  Toxicological studies have correlated inflammatory effects of diesel exhaust particles (DEP) with its organic constituents, such as the organic electrophile 1,2-naphthoquinone (1,2-NQ).
  
  
  OBJECTIVE
  To elucidate the mechanisms involved in 1,2-NQ-induced inflammatory responses, we examined the role of oxidant stress in 1,2-NQ-induced expression of inflammatory and adaptive genes in a human airway epithelial cell line.
  
  
  METHODS
  We measured cytosolic redox status and hydrogen peroxide (H2O2) in living cells using the genetically encoded green fluorescent protein (GFP)-based fluorescent indicators roGFP2 and HyPer, respectively. Expression of interleukin-8 (IL-8), cyclooxygenase-2 (COX-2), and heme oxygenase-1 (HO-1) mRNA was measured in BEAS-2B cells exposed to 1,2-NQ for 1-4 hr. Catalase overexpression and metabolic inhibitors were used to determine the role of redox changes and H2O2 in 1,2-NQ-induced gene expression.
  
  
  RESULTS
  Cells expressing roGFP2 and HyPer showed a rapid loss of redox potential and an increase in H2O2 of mitochondrial origin following exposure to 1,2-NQ. Overexpression of catalase diminished the H2O2-dependent signal but not the 1,2-NQ-induced loss of reducing potential. Catalase overexpression and inhibitors of mitochondrial respiration diminished elevations in IL-8 and COX-2 induced by exposure to 1,2-NQ, but potentiated HO-1 mRNA levels in BEAS cells.
  
  
  CONCLUSIONS
  These data show that 1,2-NQ exposure induces mitochondrial production of H2O2 that mediates the expression of inflammatory genes, but not the concurrent loss of reducing redox potential in BEAS cells. 1,2-NQ exposure also causes marked expression of HO-1 that appears to be enhanced by suppression of H2O2. These findings shed light into the oxidant-dependent events that underlie cellular responses to environmental electrophiles.
authors: Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors: Wan-Yun
authors: WY
authors: Cheng
authors: Jenna
authors: J
authors: Currier
authors: Philip A
authors: PA
authors: Bromberg
authors: Robert
authors: R
authors: Silbajoris
authors: Steven O
authors: SO
authors: Simmons
authors: James M
authors: JM
authors: Samet
mesh_terms: D000393:Air Pollutants / Q000276:immunology / Q000633:toxicity*; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics; D004782:Environmental Health / Q000379:methods; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007249:Inflammation; D016209:Interleukin-8 / Q000235:genetics; D009285:Naphthoquinones / Q000276:immunology / Q000633:toxicity*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D052638:Particulate Matter / Q000276:immunology / Q000633:toxicity; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D001335:Vehicle Emissions / Q000633:toxicity
chemical_list: D000393:Air Pollutants; D016209:Interleukin-8; D009285:Naphthoquinones; D052638:Particulate Matter; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D001335:Vehicle Emissions; D049452:Green Fluorescent Proteins; C040756:1,2-naphthoquinone; D006861:Hydrogen Peroxide; D002374:Catalase; D051547:Heme Oxygenase-1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human