Chlorobenzene Induces the NF-κ B and p38 MAP Kinase Pathways in Lung Epithelial Cells

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-κ B) and the p38 mitogen-activated protein kinase (MAPK) pathways. Human lung epithelial cells (A549) were stimulated with tumor necrosis factor (TNF)-α in the presence or absence of specific inhibitors of NF-κB 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-κ B and p38 MAP kinase and a release of the chemokine MCP-1. In the presence of IKK-NBD, a specific NF-κ 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-κ B and MAPK pathways.