mRNA induction and cytokine release of inflammatory mediators during in vitro exposure of human nasal respiratory epithelia to acetaldehyde.
Acetaldehyde has been shown to be cytotoxic and carcinogenic to the upper respiratory tract epithelium of rodents following long-term exposure. Most animal studies have concentrated on carcinogenicity and DNA-protein cross-link formation, while less is known about potential dose- and time-dependent induction of aldehyde-induced rhinitis in humans. In this in vitro study, 22 primary cell cultures established from inferior turbinate tissue of healthy individuals were exposed to acetaldehyde concentrations of 50 (German MAK value) or 500 ppm for 4 or 24 h. mRNA expression and protein levels of cytokines and other inflammatory mediators were quantified at the end of the 4- and 24-h exposures. Controls were exposed to synthetic air. Quantitative polymerase chain reaction (Q-PCR) analysis was performed for interleukin (IL)-6, IL-8, IL-1beta, monocyte chemotactic protein (MCP)-1, tumor necrosis factor (TNF)-alpha, GMCSF, Cox-1, and Cox-2. Enzyme-linked immunosorbent assay (ELISA) was performed from culture supernatants for IL-6, IL-8, IL-1beta, MCP-1, TNF-alpha, and GMCSF. Significant inductions of IL-1beta, TNF-alpha, and Cox-1 and Cox-2 mRNA were observed following exposure to > or =50 ppm acetaldehyde for 4 h. IL-6 and MCP-1 were also induced following a 4-h exposure to 500 ppm acetaldehyde. For all these parameters, effects were significantly stronger at the higher concentration. After 24-h of exposure only Cox-2 remained significantly elevated at 500 ppm but not at 50 ppm, while all other mediators had been downregulated. The obtained data suggest that with exposure to 500 ppm and remarkably also at the level of the occupational exposure limit of 50 ppm, an immediate transient upregulation of inflammatory mediator mRNA is induced, possibly leading to subclinical inflammatory effects.
Gosepath
Jan
J
Department of Otolaryngology, Head and Neck Surgery, University of Mainz, School of Medicine, Mainz, Germany. gosepath@hno.klinik.uni-mainz.de
Brieger
Juergen
J
Muttray
Axel
A
Best
Sandra
S
Pourianfar
Mehrdad
M
Jung
Detlef
D
Letzel
Stephan
S
Mann
Wolf J
WJ
D000079:Acetaldehyde / Q000494:pharmacology* / Q000633:toxicity; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D009666:Nose / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism*
D016207:Cytokines; D018836:Inflammation Mediators; D012333:RNA, Messenger; D000079:Acetaldehyde