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 characterize possible underlying mechanisms. A previous study gave evidence that expression of cyclooxygenase-2 (COX-2) is upregulated following exposure to the aromatic VOC chlorobenzene. Here, we 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, we 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 F2α (PGF2α), major products of the COX enzyme, were found to be upregulated in response to toluene, benzene or styrene exposure. Furthermore, we observed an activation of p38 MAPK resulting from aromatic VOC exposure. Treatment of the cells with a specific p38 inhibitor (SB203580) or the antioxidant N-acetylcysteine (NAC) was able to prevent the toluene/benzene/styrene-dependent COX-2 activation, and subsequent increased PGE2 and PGF2α secretion. These results suggest that toluene, benzene and styrene induce production and secretion of PGE2 and PGF2α in lung epithelial cells via p38 MAPK and COX-2 activation in a redox sensitive manner.

► This paper provides new insights into the induction of inflammatory reactions in lung cells by aromatic VOC. ► New results (never shown for any VOC so far): induction of prostaglandins E2 (PGE2) and F2 (PGF2α) by benzene, toluene and styrene. ► The VOC-induced prostaglandin release is mediated via p38 MAPK-induced COX-2 activation and initially caused by oxidative stress.