Chlorobenzene induces oxidative stress in human lung epithelial cells in vitro.
Chlorobenzene is a volatile organic compound (VOC) that is widely used as a solvent, degreasing agent and chemical intermediate in many industrial settings. Occupational studies have shown that acute and chronic exposure to chlorobenzene can cause irritation of the mucosa of the upper respiratory tract and eyes. Using in vitro assays, we have shown in a previous study that human bronchial epithelial cells release inflammatory mediators such as the cytokine monocyte chemoattractant protein-1 (MCP-1) in response to chlorobenzene. This response is mediated through the NF-kappaB signaling pathway. Here, we investigated the effects of monochlorobenzene on human lung cells, with emphasis on potential alterations of the redox equilibrium to clarify whether the chlorobenzene-induced inflammatory response in lung epithelial cells is caused via an oxidative stress-dependent mechanism. We found that expression of cellular markers for oxidative stress, such as heme oxygenase 1 (HO-1), glutathione S-transferase pi1 (GSTP1), superoxide dismutase 1 (SOD1), prostaglandin-endoperoxide synthase 2 (PTGS2) and dual specificity phosphatase 1 (DUSP1), were elevated in the presence of monochlorobenzene. Likewise, intracellular reactive oxygen species (ROS) were increased in response to exposure. However, in the presence of the antioxidants N-(2-mercaptopropionyl)-glycine (MPG) or bucillamine, chlorobenzene-induced upregulation of marker proteins and release of the inflammatory mediator MCP-1 are suppressed. These results complement our previous findings and point to an oxidative stress-mediated inflammatory response following chlorobenzene exposure.
UFZ- Helmholtz Centre for Environmental Research, Department of Environmental Immunology, Permoserstrasse 15, D-04318 Leipzig, Germany. ralph.feltens@ufz.de
Ralph
R
Feltens
Iljana
I
Mögel
Carmen
C
Röder-Stolinski
Jan-Christoph
JC
Simon
Gunda
G
Herberth
Irina
I
Lehmann
D000975:Antioxidants / Q000494:pharmacology; D015153:Blotting, Western; D002460:Cell Line; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D002722:Chlorobenzenes / Q000633:toxicity*; D004847:Epithelial Cells / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D051549:Glutathione S-Transferase pi / Q000096:biosynthesis / Q000235:genetics; D051547:Heme Oxygenase-1 / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008168:Lung / Q000166:cytology* / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects
D000975:Antioxidants; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D002722:Chlorobenzenes; D017382:Reactive Oxygen Species; D051547:Heme Oxygenase-1; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005978:Glutathione; C031294:chlorobenzene