The aromatic volatile organic compounds toluene, benzene and styrene induce COX-2 and prostaglandins in human lung epithelial cells via oxidative stress and p38 MAPK activation

Toluene, benzene and styrene are volatile organic compounds (VOCs) widely distributed in the environment. Tobacco smoke, traffic exposure and solvents used for paints, rubber and adhesives are known sources for these compounds. The aim of the present study was to investigate whether toluene, benzene and styrene can induce inflammatory reactions in lung cells and to characterise possible underlying mechanisms. A previous study gave evidence that expression of cyclooxygenase-2 (COX-2) is up-regulated following exposure to the aromatic VOC chloro-benzene. Here, the authors investigated the effects of the aromatics toluene, benzene and styrene on human lung cells, with emphasis on COX-2, the rate-limiting enzyme of the prostaglandin pathway. In addition, the authors studied the potential role of oxidative stress and p38 MAPK activation in the toluene/benzene/styrene-dependent COX-2 induction. Following exposure to the aromatic compounds, the expression level of COX-2 increased markedly. In addition, prostaglandin E2 (PGE2) and prostaglandin F2R (PGF2R), major products of the COX enzyme, were found to be up-regulated in response to toluene, benzene or styrene exposure. Furthermore, an activation of p38 MAPK resulting from aromatic VOC exposure was observed. Treatment of the cells with a specific p38 inhibitor (SB203580) or the antioxidant N-acetyl-cysteine (NAC) was able to prevent the toluene/benzene/styrene-dependent COX-2 activation, and subsequent increased PGE2 and PGF2R secretion. These results suggest that toluene, benzene and styrene induce production and secretion of PGE2 and PGF2R in lung epithelial cells via p38 MAPK and COX-2 activation in a reduction-oxidation sensitive manner.

Authors: Moegel, Iljana; Baumann, Sven; Boehme, Alexander; Kohajda, Tibor; von Bergen, Martin; Simon, Jan-Christoph; Lehmann, Irina Full Source: Toxicology [online computer file] 2011, 289(1), 28-37 (Eng) ;