TY - JOUR
T1 - A bacterial metabolite ameliorates periodontal pathogen-induced gingival epithelial barrier disruption via GPR40 signaling
AU - Yamada, Miki
AU - Takahashi, Naoki
AU - Matsuda, Yumi
AU - Sato, Keisuke
AU - Yokoji, Mai
AU - Sulijaya, Benso
AU - Maekawa, Tomoki
AU - Ushiki, Tatsuo
AU - Mikami, Yoshikazu
AU - Hayatsu, Manabu
AU - Mizutani, Yusuke
AU - Kishino, Shigenobu
AU - Ogawa, Jun
AU - Arita, Makoto
AU - Tabeta, Koichi
AU - Maeda, Takeyasu
AU - Yamazaki, Kazuhisa
N1 - Funding Information:
We thank Ms. Nahoko Kitamura and Dr. Si-Bun Park (Kyoto University, Kyoto, Japan) for preparing bioactive fatty acids. We thank Dr. Shinya Murakami (Osaka University, Osaka, Japan) for sharing the Epi 4 cells. We thank Dr. Hiroko Ida (Niigata University, Niigata, Japan) for providing technical information. This work was financially supported by JSPS KAKENHI Grant Numbers 16K11827 (to N.T.), 15H02578 and 18H04067 (to K.Y.).
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Several studies have demonstrated the remarkable properties of microbiota and their metabolites in the pathogenesis of several inflammatory diseases. 10-Hydroxy-cis-12-octadecenoic acid (HYA), a bioactive metabolite generated by probiotic microorganisms during the process of fatty acid metabolism, has been studied for its protective effects against epithelial barrier impairment in the intestines. Herein, we examined the effect of HYA on gingival epithelial barrier function and its possible application for the prevention and treatment of periodontal disease. We found that GPR40, a fatty acid receptor, was expressed on gingival epithelial cells; activation of GPR40 by HYA significantly inhibited barrier impairment induced by Porphyromonas gingivalis, a representative periodontopathic bacterium. The degradation of E-cadherin and beta-catenin, basic components of the epithelial barrier, was prevented in a GPR40-dependent manner in vitro. Oral inoculation of HYA in a mouse experimental periodontitis model suppressed the bacteria-induced degradation of E-cadherin and subsequent inflammatory cytokine production in the gingival tissue. Collectively, these results suggest that HYA exerts a protective function, through GPR40 signaling, against periodontopathic bacteria-induced gingival epithelial barrier impairment and contributes to the suppression of inflammatory responses in periodontal diseases.
AB - Several studies have demonstrated the remarkable properties of microbiota and their metabolites in the pathogenesis of several inflammatory diseases. 10-Hydroxy-cis-12-octadecenoic acid (HYA), a bioactive metabolite generated by probiotic microorganisms during the process of fatty acid metabolism, has been studied for its protective effects against epithelial barrier impairment in the intestines. Herein, we examined the effect of HYA on gingival epithelial barrier function and its possible application for the prevention and treatment of periodontal disease. We found that GPR40, a fatty acid receptor, was expressed on gingival epithelial cells; activation of GPR40 by HYA significantly inhibited barrier impairment induced by Porphyromonas gingivalis, a representative periodontopathic bacterium. The degradation of E-cadherin and beta-catenin, basic components of the epithelial barrier, was prevented in a GPR40-dependent manner in vitro. Oral inoculation of HYA in a mouse experimental periodontitis model suppressed the bacteria-induced degradation of E-cadherin and subsequent inflammatory cytokine production in the gingival tissue. Collectively, these results suggest that HYA exerts a protective function, through GPR40 signaling, against periodontopathic bacteria-induced gingival epithelial barrier impairment and contributes to the suppression of inflammatory responses in periodontal diseases.
UR - http://www.scopus.com/inward/record.url?scp=85048546466&partnerID=8YFLogxK
U2 - 10.1038/s41598-018-27408-y
DO - 10.1038/s41598-018-27408-y
M3 - Article
C2 - 29899364
AN - SCOPUS:85048546466
SN - 2045-2322
VL - 8
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 9008
ER -