Effect of TEGDMA on the activation of p38 and ERK1/2

Objectives: Dental resin monomers like triethylene glycol dimethacrylate (TEGDMA) are able to cause cytotoxicity as a result of an imbalance in cellular homeostasis. We hypothesized that the monomer might interfere with signalling cascades through stress-inducible kinases. Therefore, we analyzed the effects of TEGDMA on the activation of the MAP kinases p38 and ERK1/2.

Methods: Human THP-1 monocytes were exposed to increasing concentrations of TEGDMA in culture medium for 2h, 24h, and 48h. Then, the expression of phospho-p38 and phospho-ERK1/2 was detected and quantified by flow cytometry (FACS) after staining with specific antibodies. Lipopolysaccharide (LPS) from E. coli was used as a positive control. The data were statistically analyzed by the Mann-Whitney-U test (p<0.05).

Results: TEGDMA induced a dose-related increase of phospho-p38 and phospho-ERK1/2 expression in THP-1 cells after a 24h and 48h exposure period. After 24h, the p38 kinase was activated 1.5- and 3-fold by 3 mM and 5 mM TEGDMA compared to untreated controls. The same TEGDMA concentrations increased phospho-ERK expression by 3- and 6-fold. The activation of p38 further increased about 2-fold after a 48h exposure period, but the levels of phospho-ERK1/2 remained constant. No significant changes in expression levels compared to control cultures were detected for both kinases after a short exposure period (2h).

Conclusion: Our results suggest that the late activation of the stress kinases p38 and ERK1/2 is the response in THP-1 cells to a TEGDMA-induced imbalance of the cellular homeostasis.

Supported by the Deutsche Forschungsgemeinschaft (Schw 431/11-1)