Linking Oxidative Events to Inflammatory and Adaptive Gene Expression Induced by Exposure to an Organic Particulate Matter Component

• Published in: Environmental health perspectives Vol. 120; no. 2; pp. 267 - 274
• Main Authors: CHENG, Wan-Yun, CURRIER, Jenna, BROMBERG, Philip A, SILBAJORIS, Robert, SIMMONS, Steven O, SAMET, James M
• Format: Journal Article
• Language: English
• Published: Research Triangle Park, NC US Department of Health and Human Services 01.02.2012; National Institute of Environmental Health Sciences
• Subjects: Air Pollutants - immunology; Air Pollutants - toxicity; Biological and medical sciences; Bronchi - drug effects; Bronchi - metabolism; Catalase - metabolism; Cell Line; Cyclooxygenase 2 - genetics; Diesel motor exhaust gas; Environment. Living conditions; Environmental aspects; Environmental Health - methods; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Gene expression; Gene Expression Regulation - drug effects; Green Fluorescent Proteins - metabolism; Health aspects; Heme Oxygenase-1 - genetics; Humans; Hydrogen Peroxide - metabolism; Inflammation; Interleukin-8 - genetics; Medical sciences; Naphthoquinones - immunology; Naphthoquinones - toxicity; Oxidation-Reduction; Oxidative Stress - drug effects; Particulate Matter - immunology; Particulate Matter - toxicity; Public health. Hygiene; Public health. Hygiene-occupational medicine; Reactive Oxygen Species - metabolism; Risk factors; RNA, Messenger - metabolism; Toxicology; Vehicle Emissions - toxicity; United States; Oxidative stress; Reactive oxygen species; Organic matter; Hydrogen peroxide; Quinone; Confocal microscopy; Exposure; Inflammation; mitochondrial dysfunction; Gene expression; Real time; real-time imaging; Suspended particle; Mitochondria; Health and environment; Dysfunction; ROS; Medical imagery; quinones
• ISSN: 0091-6765; 1552-9924
• DOI: 10.1289/ehp.1104055

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). 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. 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. 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. 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.