mRNA-induction and cytokine release during in vitro exposure of human nasal respiratory epithelia to methyl methacrylate.
BACKGROUND
Methyl methacrylate (MMA) has been reported to cause histopathological changes in rodent nasal epithelium after inhalation challenges. Data in humans are lacking.


METHODS
In this in vitro design 22 primary cell cultures taken from inferior turbinate tissue of healthy individuals were exposed to MMA concentrations of 50 ppm (German MAK-value) and 200 ppm. mRNA expression and cytokine release of inflammatory mediators were quantified after 4h and after 24h. Controls were exposed to synthetic air. Q-PCR analysis was performed for TNF-alpha, IL-1beta, IL-6, IL-8, MCP-1, GMCSF, Cox-1 and Cox-2. ELISA assays were performed from culture supernatants for TNF-alpha, IL-1beta, IL-6, IL-8, MCP-1 and GMCSF.


RESULTS
Acute inductions of mRNA after 4h were observed for TNF-alpha, IL-1beta, IL-6, IL-8 and MCP-1 at 50 ppm. ELISA analysis of the described parameters did not reveal any significant upregulations at both concentrations after both 4h and 24h.


CONCLUSIONS
The obtained data suggest that exposure of human respiratory epithelia in vitro to 50 ppm and to 200 ppm of MMA does not induce lasting upregulation of the inflammatory mediators measured in this study. The exposure limit of 50 ppm appears safe following these results obtained from human respiratory epithelia.
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
D016587:Antimutagenic Agents / Q000494:pharmacology; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007378:Interleukins / Q000378:metabolism; D020366:Methylmethacrylate / Q000494:pharmacology*; D009297:Nasal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D016587:Antimutagenic Agents; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016207:Cytokines; D007378:Interleukins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D020366:Methylmethacrylate; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2