Early stress response of human nasal respiratory epithelia after exposure to 1-methoxypropanol-2

To evaluate the impact of 1-methoxypropanol-2 (MEP) for the stimulation of an inflammatory response in human respiratory mucosa, we exposed 22 primary cell cultures of nasal respiratory epithelia of healthy individuals to MEP concentrations at the level of the German MAK-value (100 ppm) and to the 10-fold concentration (1000 ppm). After 4 and 24h we analyzed the transcription of TNF-alpha, IL-1 beta, IL-6, IL-8, MCP-1, GMCSF, Cox-1 and Cox-2 by quantitative PCR as well as the release of the respective cytokines by ELISA. At both MEP concentrations we observed a significant increase of TNF-alpha-, IL-1 beta-, IL-6- and Cox-2-transcripts after 4h. After 24h cytokine transcription of TNF-alpha, IL-1 beta and IL-6 was normalized, but Cox-2 remained elevated. On the protein level IL-1 beta as well as granulocyte macrophages colony stimulating factor (GM-CSF) were decreased after 4 It or 24 h and uniquely IL-8 levels were increased after 4h. Our data suggest that MEP induces the transcription of genes encoding proinflammatory cytokines and mediators but largely not translation of those. Considering these in vitro data, existing exposure limits seem to be safe with respect to inflammatory responses of the upper respiratory tract. However, the effects of long-term exposures to MEP should be watched closely. (C) 2008 Elsevier Ireland Ltd. All rights reserved.