Chlorobenzene induces the NF-kappa B and p38 MAP kinase pathways in lung epithelial cells.
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.
Röder-Stolinski
Carmen
C
Department of Environmental Immunology, Helmholtz Centre for Environmental Research-UFZ, Leipzig, Germany.
Fischäder
Gundula
G
Oostingh
Gertie Janneke
GJ
Eder
Klaus
K
Duschl
Albert
A
Lehmann
Irina
I
D002460:Cell Line; D018932:Chemokine CCL2 / Q000378:metabolism; D002722:Chlorobenzenes / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005562:Formazans / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013778:Tetrazolium Salts / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D002722:Chlorobenzenes; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D005562:Formazans; D007093:Imidazoles; D016328:NF-kappa B; D011725:Pyridines; D012333:RNA, Messenger; D013778:Tetrazolium Salts; D014409:Tumor Necrosis Factor-alpha; C079782:MTT formazan; D048051:p38 Mitogen-Activated Protein Kinases; C031294:chlorobenzene; C093642:SB 203580; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole