Differential cytotoxicity of long-chain bases for human oral gingival epithelial keratinocytes, oral fibroblasts, and dendritic cells

Christopher Poulsen; Leslie A Mehalick; Carol L Fischer; Emily A Lanzel; Amber M Bates; Katherine S Walters; Joseph E Cavanaugh; Janet M Guthmiller; Georgia K Johnson; Philip W Wertz; Kim A Brogden

doi:10.1016/j.toxlet.2015.05.012

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Differential cytotoxicity of long-chain bases for human oral gingival epithelial keratinocytes, oral fibroblasts, and dendritic cells

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Differential cytotoxicity of long-chain bases for human oral gingival epithelial keratinocytes, oral fibroblasts, and dendritic cells

Christopher Poulsen, Leslie A Mehalick, Carol L Fischer, Emily A Lanzel, Amber M Bates, Katherine S Walters, Joseph E Cavanaugh, Janet M Guthmiller, Georgia K Johnson, Philip W Wertz, …

Toxicology letters, Vol.237(1), pp.21-29

08/19/2015

DOI: 10.1016/j.toxlet.2015.05.012

PMCID: PMC4596918

PMID: 26550599

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Abstract

•Long-chain bases sphingosine and dihydrosphingosine are in saliva and have antimicrobial activity against oral pathogens.•We determined the toxicity of sphingosine, dihydrosphingosine, and phytosphingosine for GE keratinocytes, GF, DC, and SCC cells.•The LD50 of long-chain bases for GE keratinocytes, GF, SCC cells, and DC were considerably higher than their MIC for oral pathogens.•This finding is important in pursuing the future potential of long-chain bases in treating periodontal and oral infections. 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 10.0–640.0μM 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, 0.2–10.0μM long-chain bases and GML were not cytotoxic; 40.0–80.0μM long-chain bases, but not GML, were cytotoxic; and 80.0μM long-chain bases induced cellular damage and death in less than 20min. 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.

Human oral gingival epithelial keratinocytes

Phytosphingosine

Dendritic cells

Dihydrosphingosine

Sphingosine

Cytotoxicity

Oral gingival fibroblasts

Glycerol monolaurate

Oral squamous cell carcinoma cells

Details

Title: Subtitle: Differential cytotoxicity of long-chain bases for human oral gingival epithelial keratinocytes, oral fibroblasts, and dendritic cells
Creators: Christopher Poulsen - Department of Periodontics, College of Dentistry, The University of Iowa, Iowa City, IA 52242, USA
Leslie A Mehalick - Department of Periodontics, College of Dentistry, The University of Iowa, Iowa City, IA 52242, USA
Carol L Fischer - Dows Institute for Dental Research, College of Dentistry, The University of Iowa, Iowa City, IA 52242, USA
Emily A Lanzel - Department of Oral Pathology, Radiology and Medicine, College of Dentistry, The University of Iowa, Iowa City, IA 52242, USA
Amber M Bates - Dows Institute for Dental Research, College of Dentistry, The University of Iowa, Iowa City, IA 52242, USA
Katherine S Walters - Central Microscopy Research Facility, The University of Iowa, Iowa City, IA 52242, USA
Joseph E Cavanaugh - Department of Biostatistics, College of Public Health, The University of Iowa, Iowa City, IA 52242, USA
Janet M Guthmiller - College of Dentistry, University of Nebraska Medical Center, 40th and Holdrege, Lincoln, NE 68583, USA
Georgia K Johnson - Department of Periodontics, College of Dentistry, The University of Iowa, Iowa City, IA 52242, USA
Philip W Wertz - Dows Institute for Dental Research, College of Dentistry, The University of Iowa, Iowa City, IA 52242, USA
Kim A Brogden - Department of Periodontics, College of Dentistry, The University of Iowa, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Toxicology letters, Vol.237(1), pp.21-29
DOI: 10.1016/j.toxlet.2015.05.012
PMID: 26550599
PMCID: PMC4596918
NLM abbreviation: Toxicol Lett
ISSN: 0378-4274
eISSN: 1879-3169
Publisher: Elsevier Ireland Ltd
Grant note: name: Carver College of Medicine, Holden Comprehensive Cancer Center; name: Iowa City Veteran’s Administration Medical Center
Language: English
Date published: 08/19/2015
Academic Unit: Statistics and Actuarial Science; Oral Pathology, Radiology and Medicine; Biostatistics; Injury Prevention Research Center; Dental Research; Periodontics
Record Identifier: 9983985970102771

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