PMID- 18554678 OWN - NLM STAT- MEDLINE DCOM- 20080924 LR - 20131121 IS - 1096-0333 (Electronic) IS - 0041-008X (Linking) VI - 231 IP - 2 DP - 2008 Sep 1 TI - Styrene induces an inflammatory response in human lung epithelial cells via oxidative stress and NF-kappaB activation. PG - 241-7 LID - 10.1016/j.taap.2008.04.010 [doi] AB - Styrene is a volatile organic compound (VOC) that is widely used as a solvent in many industrial settings. Chronic exposure to styrene can result in irritation of the mucosa of the upper respiratory tract. Contact of styrene with epithelial cells stimulates the expression of a variety of inflammatory mediators, including the chemotactic cytokine monocyte chemoattractant protein-1 (MCP-1). To characterise the underlying mechanisms of the induction of inflammatory signals by styrene, we investigated the influence of this compound on the induction of oxidative stress and the activation of the nuclear factor-kappa B (NF-kappaB) signalling pathway in human lung epithelial cells (A549). The results demonstrate that styrene-induced MCP-1 expression, as well as the expression of the oxidative stress marker glutathione S-transferase (GST), is associated with a concentration dependent pattern of NF-kappaB activity. An inhibitor of NF-kappaB, IKK-NBD, and the anti-inflammatory antioxidant N-acetylcysteine (NAC) were both effective in suppressing styrene-induced MCP-1 secretion. In addition, NAC was capable of inhibiting the upregulation of GST expression. Our findings suggest that the activation of the NF-kappaB signalling pathway by styrene is mediated via a redox-sensitive mechanism. FAU - Roder-Stolinski, Carmen AU - Roder-Stolinski C AD - UFZ-Helmholtz Centre for Environmental Research, Department of Environmental Immunology, Permoserstrasse 15, D-04318 Leipzig, Germany. FAU - Fischader, Gundula AU - Fischader G FAU - Oostingh, Gertie Janneke AU - Oostingh GJ FAU - Feltens, Ralph AU - Feltens R FAU - Kohse, Franziska AU - Kohse F FAU - von Bergen, Martin AU - von Bergen M FAU - Morbt, Nora AU - Morbt N FAU - Eder, Klaus AU - Eder K FAU - Duschl, Albert AU - Duschl A FAU - Lehmann, Irina AU - Lehmann I LA - eng PT - Journal Article DEP - 20080429 PL - United States TA - Toxicol Appl Pharmacol JT - Toxicology and applied pharmacology JID - 0416575 RN - 0 (Chemokine CCL2) RN - 0 (NF-kappa B) RN - 0 (Solvents) RN - 44LJ2U959V (Styrene) RN - EC 2.5.1.18 (Glutathione Transferase) SB - IM MH - Cell Line MH - Chemokine CCL2/drug effects/metabolism MH - Dose-Response Relationship, Drug MH - Epithelial Cells/drug effects MH - Gene Expression Regulation/drug effects MH - Glutathione Transferase/drug effects/metabolism MH - Humans MH - Lung/*drug effects/metabolism MH - NF-kappa B/*drug effects/metabolism MH - Oxidation-Reduction MH - Oxidative Stress/*drug effects MH - Signal Transduction/drug effects MH - Solvents/administration & dosage/*toxicity MH - Styrene/administration & dosage/*toxicity EDAT- 2008/06/17 09:00 MHDA- 2008/09/25 09:00 CRDT- 2008/06/17 09:00 PHST- 2007/11/29 00:00 [received] PHST- 2008/03/24 00:00 [revised] PHST- 2008/04/18 00:00 [accepted] PHST- 2008/06/17 09:00 [pubmed] PHST- 2008/09/25 09:00 [medline] PHST- 2008/06/17 09:00 [entrez] AID - S0041-008X(08)00181-6 [pii] AID - 10.1016/j.taap.2008.04.010 [doi] PST - ppublish SO - Toxicol Appl Pharmacol. 2008 Sep 1;231(2):241-7. doi: 10.1016/j.taap.2008.04.010. Epub 2008 Apr 29.