title: The aromatic volatile organic compounds toluene, benzene and styrene induce COX-2 and prostaglandins in human lung epithelial cells via oxidative stress and p38 MAPK activation.
abstract: Toluene, benzene and styrene are volatile organic compounds (VOCs) widely distributed in the environment. Tobacco smoke, traffic exposure and solvents used for paints, rubber and adhesives are known sources for these compounds. The aim of the present study was to investigate whether toluene, benzene and styrene can induce inflammatory reactions in lung cells and to characterize possible underlying mechanisms. A previous study gave evidence that expression of cyclooxygenase-2 (COX-2) is upregulated following exposure to the aromatic VOC chlorobenzene. Here, we investigated the effects of the aromatics toluene, benzene and styrene on human lung cells, with emphasis on COX-2, the rate-limiting enzyme of the prostaglandin pathway. In addition, we studied the potential role of oxidative stress and p38 MAPK activation in the toluene/benzene/styrene-dependent COX-2 induction. Following exposure to the aromatic compounds the expression level of COX-2 increased markedly. In addition, prostaglandin E(2) (PGE(2)) and prostaglandin F(2α) (PGF(2α)), major products of the COX enzyme, were found to be upregulated in response to toluene, benzene or styrene exposure. Furthermore, we observed an activation of p38 MAPK resulting from aromatic VOC exposure. Treatment of the cells with a specific p38 inhibitor (SB203580) or the antioxidant N-acetylcysteine (NAC) was able to prevent the toluene/benzene/styrene-dependent COX-2 activation, and subsequent increased PGE(2) and PGF(2α) secretion. These results suggest that toluene, benzene and styrene induce production and secretion of PGE(2) and PGF(2α) in lung epithelial cells via p38 MAPK and COX-2 activation in a redox sensitive manner.
authors.affiliation: UFZ - Helmholtz Centre for Environmental Research, Department of Environmental Immunology, Leipzig, Germany.
authors.forename: Iljana
authors.initials: I
authors.lastname: Mögel
authors.forename: Sven
authors.initials: S
authors.lastname: Baumann
authors.forename: Alexander
authors.initials: A
authors.lastname: Böhme
authors.forename: Tibor
authors.initials: T
authors.lastname: Kohajda
authors.forename: Martin
authors.initials: M
authors.lastname: von Bergen
authors.forename: Jan-Christoph
authors.initials: JC
authors.lastname: Simon
authors.forename: Irina
authors.initials: I
authors.lastname: Lehmann
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000393:Air Pollutants / Q000633:toxicity*; D001555:Benzene Derivatives / Q000633:toxicity*; D015153:Blotting, Western; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D004847:Epithelial Cells; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology
chemical_list: D000393:Air Pollutants; D001555:Benzene Derivatives; D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D011725:Pyridines; D015237:Dinoprost; D051546:Cyclooxygenase 2; D020930:MAP Kinase Kinase Kinases; C069937:MAP3K8 protein, human; D005978:Glutathione; D015232:Dinoprostone; C093642:SB 203580; D000111:Acetylcysteine