title: The dental monomer hydroxyethyl methacrylate (HEMA) counteracts lipopolysaccharide-induced IL-1β release-Possible role of glutathione.
abstract: Methacrylate monomers, like 2-hydroxyethyl methacrylate (HEMA), are common components of resin based dental materials. Leakage of unpolymerized monomers after placement and curing leads to human exposure. HEMA is known to inhibit lipopolysaccharide (LPS) induced cytokine release. In this study we explore a possible role of the antioxidant glutathione (GSH) in this effect. In the RAW 264.7 murine macrophage cell line, HEMA (<2mM) did not induce cell death, but reduced cellular GSH levels, increased cellular ROS and decreased the IL-1β release from LPS-stimulated cells. Moreover, the IL-1β mRNA levels were reduced after 3-6h exposure, suggesting transcriptional effects of HEMA. The GSH modulators butylsulfoximine (BSO; inhibitor of GSH synthesis) and 2-oxothiazolidine-4-carboxylate (OTC; Cysteine precursor) caused a decrease and increase in the LPS-induced IL-1β release, respectively, suggesting a role for GSH in negative regulation of LPS-induced IL-1β release. However, the magnitude and dynamics of the effects of HEMA and BSO on LPS-induced IL-1β release and GSH depletion differed considerably. Thus, GSH depletion alone could not explain the strong attenuation of LPS-induced IL-1β release caused by HEMA. Formation of HEMA-protein conjugates due to the thiol reactivity of HEMA emerges as a likely candidate for the molecular mechanism accounting for this effect.
authors.affiliation: Nordic Institute of Dental Materials, Sognsveien 70A, N-0855 Oslo, Norway; Norwegian Institute of Public Health, Domain of Infection Control and Environmental Health, P.O. Box 4404, N-0403 Oslo, Norway. Electronic address: anette.kocbach@gmail.com.
authors.forename: Anette Kocbach
authors.initials: AK
authors.lastname: Bolling
authors.affiliation: Norwegian Veterinary Institute, P.O. Box 750 Sentrum, N-0106 Oslo, Norway.
authors.forename: Anita
authors.initials: A
authors.lastname: Solhaug
authors.affiliation: Nordic Institute of Dental Materials, Sognsveien 70A, N-0855 Oslo, Norway.
authors.forename: Else
authors.initials: E
authors.lastname: Morisbak
authors.affiliation: Norwegian Institute of Public Health, Domain of Infection Control and Environmental Health, P.O. Box 4404, N-0403 Oslo, Norway.
authors.forename: Jørn A
authors.initials: JA
authors.lastname: Holme
authors.affiliation: Nordic Institute of Dental Materials, Sognsveien 70A, N-0855 Oslo, Norway.
authors.forename: Jan Tore
authors.initials: JT
authors.lastname: Samuelsen
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008689:Methacrylates / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D011761:Pyrrolidonecarboxylic Acid / Q000737:chemistry / Q000494:pharmacology; D000067996:RAW 264.7 Cells; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012117:Resins, Synthetic / Q000737:chemistry / Q000494:pharmacology*; D053778:Thiazolidines / Q000737:chemistry / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000975:Antioxidants; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D008689:Methacrylates; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D012117:Resins, Synthetic; D053778:Thiazolidines; D014409:Tumor Necrosis Factor-alpha; C005044:hydroxyethyl methacrylate; D005978:Glutathione; D011761:Pyrrolidonecarboxylic Acid; C029536:2-oxothiazolidine-4-carboxylic acid
keywords: Cytokine; Inflammation; Macrophage; Methacrylate monomers