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

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 10.0-640.0μM 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.

Original languageEnglish (US)
Pages (from-to)21-29
Number of pages9
JournalToxicology Letters
Volume237
Issue number1
DOIs
StatePublished - Aug 9 2015

Fingerprint

Fibroblasts
Cytotoxicity
Keratinocytes
Dendritic Cells
phytosphingosine
Pathogens
Sphingosine
Propidium
Confocal microscopy
Lethal Dose 50
Anti-Infective Agents
Infection
Metabolism
Confocal Microscopy
Mouth
Permeability
Membranes
monolaurin
Therapeutics

Keywords

  • Cytotoxicity
  • Dendritic cells
  • Dihydrosphingosine
  • Glycerol monolaurate
  • Human oral gingival epithelial keratinocytes
  • Oral gingival fibroblasts
  • Oral squamous cell carcinoma cells
  • Phytosphingosine
  • Sphingosine

ASJC Scopus subject areas

  • Toxicology

Cite this

Poulsen, C., Mehalick, L. A., Fischer, C. L., Lanzel, E. A., Bates, A. M., Walters, K. S., ... Brogden, K. A. (2015). Differential cytotoxicity of long-chain bases for human oral gingival epithelial keratinocytes, oral fibroblasts, and dendritic cells. Toxicology Letters, 237(1), 21-29. https://doi.org/10.1016/j.toxlet.2015.05.012

Differential cytotoxicity of long-chain bases for human oral gingival epithelial keratinocytes, oral fibroblasts, and dendritic cells. / Poulsen, Christopher; Mehalick, Leslie A.; Fischer, Carol L.; Lanzel, Emily A.; Bates, Amber M.; Walters, Katherine S.; Cavanaugh, Joseph E.; Guthmiller, Janet M; Johnson, Georgia K.; Wertz, Philip W.; Brogden, Kim A.

In: Toxicology Letters, Vol. 237, No. 1, 09.08.2015, p. 21-29.

Research output: Contribution to journalArticle

Poulsen, C, Mehalick, LA, Fischer, CL, Lanzel, EA, Bates, AM, Walters, KS, Cavanaugh, JE, Guthmiller, JM, Johnson, GK, Wertz, PW & Brogden, KA 2015, 'Differential cytotoxicity of long-chain bases for human oral gingival epithelial keratinocytes, oral fibroblasts, and dendritic cells', Toxicology Letters, vol. 237, no. 1, pp. 21-29. https://doi.org/10.1016/j.toxlet.2015.05.012
Poulsen, Christopher ; Mehalick, Leslie A. ; Fischer, Carol L. ; Lanzel, Emily A. ; Bates, Amber M. ; Walters, Katherine S. ; Cavanaugh, Joseph E. ; Guthmiller, Janet M ; Johnson, Georgia K. ; Wertz, Philip W. ; Brogden, Kim A. / Differential cytotoxicity of long-chain bases for human oral gingival epithelial keratinocytes, oral fibroblasts, and dendritic cells. In: Toxicology Letters. 2015 ; Vol. 237, No. 1. pp. 21-29.
@article{754c3669a709426b8c52124ae50d0b85,
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 10.0-640.0μM 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.",
keywords = "Cytotoxicity, Dendritic cells, Dihydrosphingosine, Glycerol monolaurate, Human oral gingival epithelial keratinocytes, Oral gingival fibroblasts, Oral squamous cell carcinoma cells, Phytosphingosine, Sphingosine",
author = "Christopher Poulsen and Mehalick, {Leslie A.} and Fischer, {Carol L.} and Lanzel, {Emily A.} and Bates, {Amber M.} and Walters, {Katherine S.} and Cavanaugh, {Joseph E.} and Guthmiller, {Janet M} and Johnson, {Georgia K.} and Wertz, {Philip W.} and Brogden, {Kim A.}",
year = "2015",
month = "8",
day = "9",
doi = "10.1016/j.toxlet.2015.05.012",
language = "English (US)",
volume = "237",
pages = "21--29",
journal = "Toxicology Letters",
issn = "0378-4274",
publisher = "Elsevier BV",
number = "1",

}

TY - JOUR

T1 - Differential cytotoxicity of long-chain bases for human oral gingival epithelial keratinocytes, oral fibroblasts, and dendritic cells

AU - Poulsen, Christopher

AU - Mehalick, Leslie A.

AU - Fischer, Carol L.

AU - Lanzel, Emily A.

AU - Bates, Amber M.

AU - Walters, Katherine S.

AU - Cavanaugh, Joseph E.

AU - Guthmiller, Janet M

AU - Johnson, Georgia K.

AU - Wertz, Philip W.

AU - Brogden, Kim A.

PY - 2015/8/9

Y1 - 2015/8/9

N2 - 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.

AB - 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.

KW - Cytotoxicity

KW - Dendritic cells

KW - Dihydrosphingosine

KW - Glycerol monolaurate

KW - Human oral gingival epithelial keratinocytes

KW - Oral gingival fibroblasts

KW - Oral squamous cell carcinoma cells

KW - Phytosphingosine

KW - Sphingosine

UR - http://www.scopus.com/inward/record.url?scp=84930940063&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84930940063&partnerID=8YFLogxK

U2 - 10.1016/j.toxlet.2015.05.012

DO - 10.1016/j.toxlet.2015.05.012

M3 - Article

C2 - 26005054

AN - SCOPUS:84930940063

VL - 237

SP - 21

EP - 29

JO - Toxicology Letters

JF - Toxicology Letters

SN - 0378-4274

IS - 1

ER -