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Endothelin Regulates Porphyromonas gingivalis-Induced Production of Inflammatory Cytokines

 Ga-Yeon Son  ;  Eun-Jung Bak  ;  Ji-Hye Kim  ;  Dong Eun Lee  ;  Si-Mook Kang  ;  So Yun Lee  ;  Lin Choi  ;  Ji Su Sun  ;  Seul Ki Kim  ;  Wonse Park  ;  Baek Il Kim  ;  Yun-Jung Yoo  ;  Inik Chang  ;  Dong Min Shin 
 PLOS ONE, Vol.11(12) : e0167713, 2016 
Journal Title
Issue Date
Periodontitis is a very common oral inflammatory disease that results in the destruction of supporting connective and osseous tissues of the teeth. Although the exact etiology is still unclear, Gram-negative bacteria, especially Porphyromonas gingivalis in subgingival pockets are thought to be one of the major etiologic agents of periodontitis. Endothelin (ET) is a family of three 21-amino acid peptides, ET-1, -2, and -3, that activate G protein-coupled receptors, ETA and ETB. Endothelin is involved in the occurrence and progression of various inflammatory diseases. Previous reports have shown that ET-1 and its receptors, ETA and ETB are expressed in the periodontal tissues and, that ET-1 levels in gingival crevicular fluid are increased in periodontitis patients. Moreover, P. gingivalis infection has been shown to induce the production of ET-1 along with other inflammatory cytokines. Despite these studies, however, the functional significance of endothelin in periodontitis is still largely unknown. In this study, we explored the cellular and molecular mechanisms of ET-1 action in periodontitis using human gingival epithelial cells (HGECs). ET-1 and ETA, but not ETB, were abundantly expressed in HGECs. Stimulation of HGECs with P. gingivalis or P. gingivalis lipopolysaccharide increased the expression of ET-1 and ETA suggesting the activation of the endothelin signaling pathway. Production of inflammatory cytokines, IL-1β, TNFα, and IL-6, was significantly enhanced by exogenous ET-1 treatment, and this effect depended on the mitogen-activated protein kinases via intracellular Ca2+ increase, which resulted from the activation of the phospholipase C/inositol 1,4,5-trisphosphate pathway. The inhibition of the endothelin receptor-mediated signaling pathway with the dual receptor inhibitor, bosentan, partially ameliorated alveolar bone loss and immune cell infiltration. These results suggest that endothelin plays an important role in P. gingivalis-mediated periodontitis. Thus, endothelin antagonism may be a potential therapeutic approach for periodontitis treatment.
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2. College of Dentistry (치과대학) > Dept. of Advanced General Dentistry (통합치의학과) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Preventive Dentistry and Public Oral Health (예방치과학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Others (기타) > 1. Journal Papers
Yonsei Authors
Kang, Si-Mook(강시묵) ORCID logo https://orcid.org/0000-0003-2341-3636
Kim, Baek Il(김백일) ORCID logo https://orcid.org/0000-0001-8234-2327
Park, Wonse(박원서) ORCID logo https://orcid.org/0000-0002-2081-1156
Shin, Dong Min(신동민) ORCID logo https://orcid.org/0000-0001-6042-0435
Yoo, Yun Jung(유윤정) ORCID logo https://orcid.org/0000-0002-0045-9597
Chang, In Ik(장인익)
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