title: Carboxylesterase expression in human dental pulp cells: role in regulation of BisGMA-induced prostanoid production and cytotoxicity.
abstract: Biocompatibility of dentin bonding agents (DBA) and composite resin may affect the treatment outcome (e.g., healthy pulp, pulpal inflammation, pulp necrosis) after operative restoration. Bisphenol-glycidyl methacrylate (BisGMA) is one of the major monomers present in DBA and resin. Prior studies focused on salivary esterase for metabolism and degradation of resin monomers clinically. This study found that human dental pulp cells expressed mainly carboxylesterase-2 (CES2) and smaller amounts of CES1A1 and CES3 isoforms. Exposure to BisGMA stimulated CES isoforms expression of pulp cells, and this event was inhibited by catalase. Exogenous addition of porcine esterase prevented BisGMA- and DBA-induced cytotoxicity. Interestingly, inhibition of CES by bis(p-nitrophenyl) phosphate (BNPP) and CES2 by loperamide enhanced the cytotoxicity of BisGMA and DBA. Addition of porcine esterase or N-acetyl-l-cysteine prevented BisGMA-induced prostaglandin E(2) (PGE(2)) and PGF(2α) production. In contrast, addition of BNPP and loperamide, but not mevastatin, enhanced BisGMA-induced PGE(2) and PGF(2α) production in dental pulp cells. These results suggest that BisGMA may induce the cytotoxicity and prostanoid production of pulp cells, leading to pulpal inflammation or necrosis via reactive oxygen species production. Expression of CES, especially CES2, in dental pulp cells can be an adaptive response to protect dental pulp against BisGMA-induced cytotoxicity and prostanoid release. Resin monomers are the main toxic components in DBA, and the ester group is crucial for monomer toxicity.
authors.affiliation: Biomedical Science Team, Chang Gung University of Science and Technology, Taoyuan, Taiwan.
authors.forename: M-C
authors.initials: MC
authors.lastname: Chang
authors.forename: L-D
authors.initials: LD
authors.lastname: Lin
authors.forename: F-H
authors.initials: FH
authors.lastname: Chuang
authors.forename: C-P
authors.initials: CP
authors.lastname: Chan
authors.forename: T-M
authors.initials: TM
authors.lastname: Wang
authors.forename: J-J
authors.initials: JJ
authors.lastname: Lee
authors.forename: P-Y
authors.initials: PY
authors.lastname: Jeng
authors.forename: W-Y
authors.initials: WY
authors.lastname: Tseng
authors.forename: H-J
authors.initials: HJ
authors.lastname: Lin
authors.forename: J-H
authors.initials: JH
authors.lastname: Jeng
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000930:Antidiarrheals / Q000494:pharmacology; D017438:Bisphenol A-Glycidyl Methacrylate / Q000009:adverse effects* / Q000494:pharmacology; D043182:Carboxylesterase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D002478:Cells, Cultured; D002648:Child; D003603:Cytotoxins / Q000009:adverse effects* / Q000494:pharmacology; D003782:Dental Pulp / Q000201:enzymology* / Q000473:pathology; D017220:Dentin-Bonding Agents / Q000009:adverse effects* / Q000494:pharmacology; D015237:Dinoprost / Q000096:biosynthesis*; D015232:Dinoprostone / Q000096:biosynthesis*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000201:enzymology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008139:Loperamide / Q000494:pharmacology; D008297:Male; D008422:Materials Testing / Q000379:methods; D009596:Nitrophenols / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013552:Swine
chemical_list: D000930:Antidiarrheals; D003603:Cytotoxins; D017220:Dentin-Bonding Agents; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D009596:Nitrophenols; D017382:Reactive Oxygen Species; D017438:Bisphenol A-Glycidyl Methacrylate; C002887:bis(4-nitrophenyl)phosphate; D008139:Loperamide; D015237:Dinoprost; D043182:Carboxylesterase; D015232:Dinoprostone