Styrene induces an inflammatory response in human lung epithelial cells via oxidative stress and NF-kappaB activation.
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.
UFZ-Helmholtz Centre for Environmental Research, Department of Environmental Immunology, Permoserstrasse 15, D-04318 Leipzig, Germany.
Carmen
C
Röder-Stolinski
Gundula
G
Fischäder
Gertie Janneke
GJ
Oostingh
Ralph
R
Feltens
Franziska
F
Kohse
Martin
M
von Bergen
Nora
N
Mörbt
Klaus
K
Eder
Albert
A
Duschl
Irina
I
Lehmann
D002460:Cell Line; D018932:Chemokine CCL2 / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005982:Glutathione Transferase / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D012997:Solvents / Q000008:administration & dosage / Q000633:toxicity*; D020058:Styrene / Q000008:administration & dosage / Q000633:toxicity*
D018932:Chemokine CCL2; D016328:NF-kappa B; D012997:Solvents; D020058:Styrene; D005982:Glutathione Transferase