Sensitization Potential of Dental Resins: 2-Hydroxyethyl Methacrylate and Its Water-Soluble Oligomers Have Immunostimulatory Effects

Abstract

The immunostimulatory effects of the representative dental resin monomer 2-hydroxyethyl methacrylate (HEMA), a HEMA derivative that does not contain a double bond (2-hydroxyethyl isobutyrate, HEIB), and polymerized water-soluble oligomers of HEMA (PHEMA) were investigated. It is known that expression levels of either or both of CD54 and CD86 in THP-1 cells are increased by exposure to sensitizing substances. In this study, the expression levels of CD54 and CD86, the production of reactive oxygen species (ROS), and the viability of the cells were measured after 24 h of incubation with these materials at different concentrations. The concentrations of the materials that induced the expression of both CD54 and CD86 were low in the following order: NiSO4, HEMA, and methyl methacrylate (MMA). These results indicate that these dental resin monomers have lower sensitizing potentials than NiSO4. Although HEIB, which lacks a double bond, resulted in negligible ROS production and reduced cytotoxicity than HEMA, it induced the expression of CD54 and CD86. Comparison of the results for HEMA and HEIB indicates that dental resin monomer-induced sensitization may be related not only to the oxidative stress related to the methacryloyl group but also to the structures of these compounds. Of particular interest is the result that a water-soluble PHEMA oligomer with a relatively high-molecular weight also exhibited negligible cytotoxicity, whereas the expression level of CD54 increased after exposure to PHEMA at a high concentration. This result serves as a warning that polymerized substances also have the potential to induce sensitization. This study provides insight into the nature of allergic responses to dental resin materials in clinical use and may facilitate the development of more biocompatible restorative materials in the future.

Increasing the repeating units of ethylene glycol‐based dimethacrylates directed toward reduced oxidative stress and co‐stimulatory factors expression in human monocytic cells

“…(B)]. This tendency is similar to methyl methacrylate . However, the expression profile of CD86 in THP‐1 cells treated with PEG‐DMAs was not overlapped unlike the cytotoxicity profile.…”

“…We have previously investigated the co-stimulatory factor expression of THP-1 cells treated with HEMA and low molecular weight water-soluble PHEMAs. 11 It is revealed that the treatment of THP-1 cells with HEMA induces the cytotoxicity and the expression of co-stimulatory factors, although at a high concentration (400 lg/mL) than needed for nickel ion (50 lg/mL), a well-known sensitizing agent. This result suggests that the sensitization potential of HEMA is weak compared with nickel ion.…”

“…We have previously demonstrated the comparison study to verify the sensitization potential of HEMA and its water‐soluble polymers by in vitro sensitization test, called human cell line activation test . This in vitro sensitization test is based on monitoring the expression levels of CD54 and CD86 in THP‐1 cells upon the exposure of sensitizing substances .…”

“…We have previously demonstrated the comparison study to verify the sensitization potential of HEMA and its watersoluble polymers by in vitro sensitization test, called human cell line activation test. 11 This in vitro sensitization test is based on monitoring the expression levels of CD54 and CD86 in THP-1 cells upon the exposure of sensitizing substances. [12][13][14][15][16] As a result, the concentrations of the HEMA that induced the expression of both CD54 and CD86 in THP-1 cells were found to be higher than the levels for these cells treated with nickel ion, indicating that the HEMA is thought to be lower sensitization than nickel ion.…”

Structure-cytotoxicity relationship of methacrylate-based resin monomers as evaluated by an anti-oxidant responsive element-luciferase reporter assay

“…MMA has relatively good biocompatibility, and methacrylate derivatives with several functional groups have been developed for various applications and are widely used. However, it has been shown that these polymers contain 3-5% residual monomers 1,2) that could damage tissues [3][4][5][6][7] . For development of biologically satisfactory dental materials, it is important to clarify how residual monomers affect living cells and how the monomer structures are related to their cytotoxicity.…”