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Published in: BMC Oral Health 1/2019

Open Access 01-12-2019 | Research article

Anti-inflammatory effects of olanexidine gluconate on oral epithelial cells

Authors: Takuya Nii, Hiromichi Yumoto, Katsuhiko Hirota, Yoichiro Miyake

Published in: BMC Oral Health | Issue 1/2019

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Abstract

Background

Periodontitis is a biofilm-induced chronic inflammatory condition of the periodontium. Chemokines produced by the innate and acquired immune responses play a significant role in disease progression. Reducing biofilm formation and inflammatory response caused by chemokines is vital for preventing and treating periodontitis. Previously, we observed that treatment with 0.1% olanexidine gluconate (OLG) inhibited biofilm formation on saliva-coated hydroxyapatite. This study aimed to evaluate the anti-inflammatory effect of OLG on oral epithelial cells.

Methods

We examined if OLG could inhibit the inflammatory responses caused by Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS) and heat-killed P. gingivalis in immortalized human oral keratinocytes (RT7).

Results

Treatment of RT7 with non-cytotoxic OLG concentrations significantly inhibited the production of inflammatory chemokines such as interleukin 8 (IL-8), C-C motif ligand 20 (CCL20), and growth-related oncogene protein-α (GRO-α), which are stimulated by P. gingivalis LPS in a concentration-dependent manner. Moreover, the inhibitory effects were observed regardless of the treatment time with P. gingivalis LPS (6, 12, or 24 h). OLG also significantly inhibited chemokine production stimulated by heat-killed P. gingivalis.

Conclusions

The findings of this study suggest that treatment with OLG inhibits chronic inflammatory reactions in oral mucosal cells, such as periodontitis, caused by oral bacteria.
Literature
1.
go back to reference Offenbacher S. Periodontal diseases: pathogenesis. Ann Periodontol. 1996;1:821–78.CrossRef Offenbacher S. Periodontal diseases: pathogenesis. Ann Periodontol. 1996;1:821–78.CrossRef
2.
go back to reference Hirschfeld M, Weis JJ, Toshchakov V, Salkowski CA, Cody MJ, Ward DC, et al. Signaling by toll-like receptor 2 and 4 agonists results in differential gene expression in murine macrophages. Infect Immun. 2001;69:1477–82.CrossRef Hirschfeld M, Weis JJ, Toshchakov V, Salkowski CA, Cody MJ, Ward DC, et al. Signaling by toll-like receptor 2 and 4 agonists results in differential gene expression in murine macrophages. Infect Immun. 2001;69:1477–82.CrossRef
3.
go back to reference Holt SC, Kesavalu L, Walker S, Genco CA. Virulence factors of Porphyromonas gingivalis. Periodontol 2000. 1999;20:168–238.CrossRef Holt SC, Kesavalu L, Walker S, Genco CA. Virulence factors of Porphyromonas gingivalis. Periodontol 2000. 1999;20:168–238.CrossRef
4.
go back to reference Ren L, Leung WK, Darveau RP, Jin L. The expression profile of lipopolysaccharide-binding protein, membrane-bound CD14, and toll-like receptors 2 and 4 in chronic periodontitis. J Periodontol. 2005;76:1950–9.CrossRef Ren L, Leung WK, Darveau RP, Jin L. The expression profile of lipopolysaccharide-binding protein, membrane-bound CD14, and toll-like receptors 2 and 4 in chronic periodontitis. J Periodontol. 2005;76:1950–9.CrossRef
5.
go back to reference Kusumoto Y, Hirano H, Saitoh K, Yamada S, Takedachi M, Nozaki T, et al. Human gingival epithelial cells produce chemotactic factors interleukin-8 and monocyte chemo attractant protein-1 after stimulation with Porphyromonas gingivalis via toll-like receptor 2. J Periodontol. 2004;75:370–9.CrossRef Kusumoto Y, Hirano H, Saitoh K, Yamada S, Takedachi M, Nozaki T, et al. Human gingival epithelial cells produce chemotactic factors interleukin-8 and monocyte chemo attractant protein-1 after stimulation with Porphyromonas gingivalis via toll-like receptor 2. J Periodontol. 2004;75:370–9.CrossRef
6.
go back to reference Sugawara Y, Uehara A, Fujimoto Y, Kusumoto S, Fukase K, Shibata K, et al. Toll-like receptors, NOD1, and NOD2 in oral epithelial cells. J Dent Res. 2006;85:524–9.CrossRef Sugawara Y, Uehara A, Fujimoto Y, Kusumoto S, Fukase K, Shibata K, et al. Toll-like receptors, NOD1, and NOD2 in oral epithelial cells. J Dent Res. 2006;85:524–9.CrossRef
7.
go back to reference Beklen A, Hukkanen M, Richardson R, Konttinen YT. Immunohistochemical localization of toll-like receptors 1-10 in periodontitis. Oral Microbiol Immunol. 2008;23:425–31.CrossRef Beklen A, Hukkanen M, Richardson R, Konttinen YT. Immunohistochemical localization of toll-like receptors 1-10 in periodontitis. Oral Microbiol Immunol. 2008;23:425–31.CrossRef
8.
9.
go back to reference Mitchell GB, Albright BN, Caswell JL. Effect of interleukin-8 and granulocyte colony-stimulating factor on priming and activation of bovine neutrophils. Infect Immun. 2003;71:1643–9.CrossRef Mitchell GB, Albright BN, Caswell JL. Effect of interleukin-8 and granulocyte colony-stimulating factor on priming and activation of bovine neutrophils. Infect Immun. 2003;71:1643–9.CrossRef
10.
go back to reference Baggiolini M, Dewald B, Moser B. Interleukin-8 and related chemotactic cytokines--CXC and CC chemokines. Adv Immunol. 1994;55:97–179.CrossRef Baggiolini M, Dewald B, Moser B. Interleukin-8 and related chemotactic cytokines--CXC and CC chemokines. Adv Immunol. 1994;55:97–179.CrossRef
11.
go back to reference Moser B, Clark-Lewis I, Zwahlen R, Baggiolini M. Neutrophil-activating properties of the melanoma growth-stimulatory activity. J Exp Med. 1990;171:1797–802.CrossRef Moser B, Clark-Lewis I, Zwahlen R, Baggiolini M. Neutrophil-activating properties of the melanoma growth-stimulatory activity. J Exp Med. 1990;171:1797–802.CrossRef
12.
go back to reference Lombardo Bedran TB, Palomari Spolidorio D, Grenier D. Green tea polyphenol epigallocatechin-3-gallate and cranberry proanthocyanidins act in synergy with cathelicidin (LL-37) to reduce the LPS-induced inflammatory response in a three-dimensional co-culture model of gingival epithelial cells and fibroblasts. Arch Oral Biol. 2015;60:845–53.CrossRef Lombardo Bedran TB, Palomari Spolidorio D, Grenier D. Green tea polyphenol epigallocatechin-3-gallate and cranberry proanthocyanidins act in synergy with cathelicidin (LL-37) to reduce the LPS-induced inflammatory response in a three-dimensional co-culture model of gingival epithelial cells and fibroblasts. Arch Oral Biol. 2015;60:845–53.CrossRef
13.
go back to reference Cardoso CR, Garlet GP, Crippa GE, Rosa AL, Júnior WM, Rossi MA, et al. Evidence of the presence of T helper type 17 cells in chronic lesions of human periodontal disease. Oral Microbiol Immunol. 2009;24:1–6.CrossRef Cardoso CR, Garlet GP, Crippa GE, Rosa AL, Júnior WM, Rossi MA, et al. Evidence of the presence of T helper type 17 cells in chronic lesions of human periodontal disease. Oral Microbiol Immunol. 2009;24:1–6.CrossRef
14.
go back to reference Hirota K, Yoshitomi H, Hashimoto M, Maeda S, Teradaira S, Sugimoto N, et al. Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal model. J Exp Med. 2007;204:2803–12.CrossRef Hirota K, Yoshitomi H, Hashimoto M, Maeda S, Teradaira S, Sugimoto N, et al. Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal model. J Exp Med. 2007;204:2803–12.CrossRef
15.
go back to reference Hosokawa Y, Nakanishi T, Yamaguchi D, Takahashi K, Yumoto H, Ozaki K, et al. Macrophage inflammatory protein 3alpha-CC chemokine receptor 6 interactions play an important role in CD4+ T-cell accumulation in periodontal diseased tissue. Clin Exp Immunol. 2002;128:548–54.CrossRef Hosokawa Y, Nakanishi T, Yamaguchi D, Takahashi K, Yumoto H, Ozaki K, et al. Macrophage inflammatory protein 3alpha-CC chemokine receptor 6 interactions play an important role in CD4+ T-cell accumulation in periodontal diseased tissue. Clin Exp Immunol. 2002;128:548–54.CrossRef
16.
go back to reference Nakata H, Tsubotani Y, Nii T, Hagi A, Inoue Y, Imamura T. Effects of olanexidine gluconate on preoperative skin preparation: an experimental study in cynomolgus monkeys. J Med Microbiol. 2017;66:678–85.CrossRef Nakata H, Tsubotani Y, Nii T, Hagi A, Inoue Y, Imamura T. Effects of olanexidine gluconate on preoperative skin preparation: an experimental study in cynomolgus monkeys. J Med Microbiol. 2017;66:678–85.CrossRef
17.
go back to reference Hagi A, Iwata K, Nii T, Nakata H, Tsubotani Y, Inoue Y. Bactericidal effects and mechanism of action of olanexidine gluconate, a new antiseptic. Antimicrob Agents Chemother. 2015;59:4551–9.CrossRef Hagi A, Iwata K, Nii T, Nakata H, Tsubotani Y, Inoue Y. Bactericidal effects and mechanism of action of olanexidine gluconate, a new antiseptic. Antimicrob Agents Chemother. 2015;59:4551–9.CrossRef
18.
go back to reference Inoue Y, Hagi A, Nii T, Tsubotani Y, Nakata H, Iwata K. Novel antiseptic compound OPB-2045G shows potent bactericidal activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus both in vitro and in vivo: a pilot study in animals. J Med Microbiol. 2015;64:32–6.CrossRef Inoue Y, Hagi A, Nii T, Tsubotani Y, Nakata H, Iwata K. Novel antiseptic compound OPB-2045G shows potent bactericidal activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus both in vitro and in vivo: a pilot study in animals. J Med Microbiol. 2015;64:32–6.CrossRef
19.
go back to reference Fujimoto R, Kamata N, Yokoyama K, Taki M, Tomonari M, Tsutsumi S, et al. Establishment of immortalized human oral keratinocytes by gene transfer of a telomerase component. J Jpn Oral Muco Membr. 2002;8:1–8.CrossRef Fujimoto R, Kamata N, Yokoyama K, Taki M, Tomonari M, Tsutsumi S, et al. Establishment of immortalized human oral keratinocytes by gene transfer of a telomerase component. J Jpn Oral Muco Membr. 2002;8:1–8.CrossRef
20.
go back to reference Sugiyama A, Uehara A, Iki K, Matsushita K, Nakamura R, Ogawa T, et al. Activation of human gingival epithelial cells by cell-surface components of black-pigmented bacteria: augmentation of production of interleukin-8, granulocyte colony stimulating factor and granulocyte-macrophage colony-stimulating factor and expression of intercellular adhesion molecule 1. J Med Microbiol. 2002;51:27–33.CrossRef Sugiyama A, Uehara A, Iki K, Matsushita K, Nakamura R, Ogawa T, et al. Activation of human gingival epithelial cells by cell-surface components of black-pigmented bacteria: augmentation of production of interleukin-8, granulocyte colony stimulating factor and granulocyte-macrophage colony-stimulating factor and expression of intercellular adhesion molecule 1. J Med Microbiol. 2002;51:27–33.CrossRef
21.
go back to reference Ohta K, Laborde NJ, Kajiya M, Shin J, Zhu T, Thondukolam AK, et al. Expression and possible immune-regulatory function of ghrelin in oral epithelium. J Dent Res. 2011;90:1286–92.CrossRef Ohta K, Laborde NJ, Kajiya M, Shin J, Zhu T, Thondukolam AK, et al. Expression and possible immune-regulatory function of ghrelin in oral epithelium. J Dent Res. 2011;90:1286–92.CrossRef
22.
go back to reference Stathopoulou PG, Benakanakere MR, Galicia JC, Kinane DF. Epithelial cell pro-inflammatory cytokine response differs across dental plaque bacterial species. J Clin Periodontol. 2010;37:24–9.CrossRef Stathopoulou PG, Benakanakere MR, Galicia JC, Kinane DF. Epithelial cell pro-inflammatory cytokine response differs across dental plaque bacterial species. J Clin Periodontol. 2010;37:24–9.CrossRef
23.
go back to reference Jenkins S, Addy M, Wade W. The mechanism of action of chlorhexidine. A study of plaque growth on enamel inserts in vivo. J Clin Periodontol. 1988;15:415–24.CrossRef Jenkins S, Addy M, Wade W. The mechanism of action of chlorhexidine. A study of plaque growth on enamel inserts in vivo. J Clin Periodontol. 1988;15:415–24.CrossRef
24.
go back to reference Millhouse E, Jose A, Sherry L, Lappin DF, Patel N, Middleton AM, et al. Development of an in vitro periodontal biofilm model for assessing antimicrobial and host modulatory effects of bioactive molecules. BMC Oral Health. 2014;14:80.CrossRef Millhouse E, Jose A, Sherry L, Lappin DF, Patel N, Middleton AM, et al. Development of an in vitro periodontal biofilm model for assessing antimicrobial and host modulatory effects of bioactive molecules. BMC Oral Health. 2014;14:80.CrossRef
Metadata
Title
Anti-inflammatory effects of olanexidine gluconate on oral epithelial cells
Authors
Takuya Nii
Hiromichi Yumoto
Katsuhiko Hirota
Yoichiro Miyake
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Oral Health / Issue 1/2019
Electronic ISSN: 1472-6831
DOI
https://doi.org/10.1186/s12903-019-0932-0

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