Endothelin Regulates Porphyromonas gingivalis-Induced Production of Inflammatory Cytokines.
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 o...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5193354?pdf=render |
| _version_ | 1819059246517452800 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Ga-Yeon Son |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T14:08:03Z |
| format | Article |
| id | doaj.art-0203dbe6bfcb4c27aeef0f5f5a94c3b6 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T14:08:03Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-0203dbe6bfcb4c27aeef0f5f5a94c3b62022-12-21T19:01:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-011112e016771310.1371/journal.pone.0167713Endothelin Regulates Porphyromonas gingivalis-Induced Production of Inflammatory Cytokines.Ga-Yeon SonEun-Jung BakJi-Hye KimDong Eun LeeSi-Mook KangSo Yun LeeLin ChoiJi Su SunSeul Ki KimWonse ParkBaek Il KimYun-Jung YooInik ChangDong Min ShinPeriodontitis 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.http://europepmc.org/articles/PMC5193354?pdf=render |
| spellingShingle | 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 Endothelin Regulates Porphyromonas gingivalis-Induced Production of Inflammatory Cytokines. PLoS ONE |
| title | Endothelin Regulates Porphyromonas gingivalis-Induced Production of Inflammatory Cytokines. |
| title_full | Endothelin Regulates Porphyromonas gingivalis-Induced Production of Inflammatory Cytokines. |
| title_fullStr | Endothelin Regulates Porphyromonas gingivalis-Induced Production of Inflammatory Cytokines. |
| title_full_unstemmed | Endothelin Regulates Porphyromonas gingivalis-Induced Production of Inflammatory Cytokines. |
| title_short | Endothelin Regulates Porphyromonas gingivalis-Induced Production of Inflammatory Cytokines. |
| title_sort | endothelin regulates porphyromonas gingivalis induced production of inflammatory cytokines |
| url | http://europepmc.org/articles/PMC5193354?pdf=render |
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