title: Differential cytotoxicity of long-chain bases for human oral gingival epithelial keratinocytes, oral fibroblasts, and dendritic cells.
abstract: Long-chain bases are present in the oral cavity. Previously we determined that sphingosine, dihydrosphingosine, and phytosphingosine have potent antimicrobial activity against oral pathogens. Here, we determined the cytotoxicities of long-chain bases for oral cells, an important step in considering their potential as antimicrobial agents for oral infections. This information would clearly help in establishing prophylactic or therapeutic doses. To assess this, human oral gingival epithelial (GE) keratinocytes, oral gingival fibroblasts (GF), and dendritic cells (DC) were exposed to 10.0-640.0 μM long-chain bases and glycerol monolaurate (GML). The effects of long-chain bases on cell metabolism (conversion of resazurin to resorufin), membrane permeability (uptake of propidium iodide or SYTOX-Green), release of cellular contents (LDH), and cell morphology (confocal microscopy) were all determined. GE keratinocytes were more resistant to long-chain bases as compared to GF and DC, which were more susceptible. For DC, 0.2-10.0 μM long-chain bases and GML were not cytotoxic; 40.0-80.0 μM long-chain bases, but not GML, were cytotoxic; and 80.0 μM long-chain bases induced cellular damage and death in less than 20 min. The LD50 of long-chain bases for GE keratinocytes, GF, and DC were considerably higher than their minimal inhibitory concentrations for oral pathogens, a finding important to pursuing their future potential in treating periodontal and oral infections.
authors.affiliation: Department of Periodontics, College of Dentistry, The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Poulsen
authors.affiliation: Department of Periodontics, College of Dentistry, The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Mehalick
authors.affiliation: Dows Institute for Dental Research, College of Dentistry, The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Carol L
authors.initials: CL
authors.lastname: Fischer
authors.affiliation: Department of Oral Pathology, Radiology and Medicine, College of Dentistry, The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Lanzel
authors.affiliation: Dows Institute for Dental Research, College of Dentistry, The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Amber M
authors.initials: AM
authors.lastname: Bates
authors.affiliation: Central Microscopy Research Facility, The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Walters
authors.affiliation: Department of Biostatistics, College of Public Health, The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Cavanaugh
authors.affiliation: College of Dentistry, University of Nebraska Medical Center, 40th and Holdrege, Lincoln, NE 68583, USA.
authors.forename: Janet M
authors.initials: JM
authors.lastname: Guthmiller
authors.affiliation: Department of Periodontics, College of Dentistry, The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Georgia K
authors.initials: GK
authors.lastname: Johnson
authors.affiliation: Dows Institute for Dental Research, College of Dentistry, The University of Iowa, Iowa City, IA 52242, USA; Department of Oral Pathology, Radiology and Medicine, College of Dentistry, The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Philip W
authors.initials: PW
authors.lastname: Wertz
authors.affiliation: Department of Periodontics, College of Dentistry, The University of Iowa, Iowa City, IA 52242, USA; Dows Institute for Dental Research, College of Dentistry, The University of Iowa, Iowa City, IA 52242, USA. Electronic address: kim-brogden@uiowa.edu.
authors.forename: Kim A
authors.initials: KA
authors.lastname: Brogden
mesh_terms: D000890:Anti-Infective Agents / Q000633:toxicity; D002454:Cell Differentiation / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005881:Gingiva / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D007928:Lethal Dose 50; D012463:Saliva / Q000737:chemistry; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000633:toxicity*
chemical_list: D000890:Anti-Infective Agents; D013110:Sphingosine; C005682:safingol
keywords: Cytotoxicity; Dendritic cells; Dihydrosphingosine; Glycerol monolaurate; Human oral gingival epithelial keratinocytes; Oral gingival fibroblasts; Oral squamous cell carcinoma cells; Phytosphingosine; Sphingosine