Title: | Chlorobenzene induces the NF-kappa B and p38 MAP kinase pathways in lung epithelial cells |
Author(s): | Roder-Stolinski C; Fischader G; Oostingh GJ; Eder K; Duschl A; Lehmann I; |
Address: | "Department of Environmental Immunology, Helmholtz Centre for Environmental Research-UFZ, Leipzig, Germany" |
DOI: | 10.1080/08958370802020810 |
ISSN/ISBN: | 1091-7691 (Electronic) 0895-8378 (Linking) |
Abstract: | "Chlorobenzene is a volatile organic compound that is used as a solvent in many industrial settings and has been shown to be related with irritations of the respiratory tract. Exposure to chlorobenzene induces the release of monocyte chemoattractant protein 1 (MCP-1) by lung epithelial cells, a chemokine involved in inflammatory reactions. To characterize the underlying mechanisms we investigated the influence of chlorobenzene on the activation of two intracellular signalling pathways: the nuclear factor-kappa B (NF-kappa B) and the p38 mitogen-activated protein kinase (MAPK) pathways. Human lung epithelial cells (A549) were stimulated with tumor necrosis factor (TNF)-alpha in the presence or absence of specific inhibitors of NF-kappaB or the p38 MAP kinase and exposed to chlorobenzene using an air-liquid cell culture system. Exposure of lung epithelial cells to chlorobenzene resulted in an activation of NF-kappa B and p38 MAP kinase and a release of the chemokine MCP-1. In the presence of IKK-NBD, a specific NF-kappa B inhibitor, or the inhibitors of the p38 MAP kinase SB 203580 and SB 202190, the chlorobenzene-related MCP-1 release was suppressed, suggesting an involvement of both pathways in the chlorobenzene induced expression of MCP-1. Our data show that the release of MCP-1 following chlorobenzene exposure is dependent on the NF-kappa B and MAPK pathways" |
Keywords: | "Cell Line Chemokine CCL2/metabolism Chlorobenzenes/*toxicity Dose-Response Relationship, Drug Drug Combinations Enzyme Inhibitors/pharmacology Formazans/metabolism Gene Expression/drug effects Humans Imidazoles/pharmacology NF-kappa B/antagonists & inhibi;" |
Notes: | "MedlineRoder-Stolinski, Carmen Fischader, Gundula Oostingh, Gertie Janneke Eder, Klaus Duschl, Albert Lehmann, Irina eng England 2008/07/23 Inhal Toxicol. 2008 Jul; 20(9):813-20. doi: 10.1080/08958370802020810" |