title: Secreted caveolin-1 enhances periodontal inflammation by targeting gingival fibroblasts.
abstract: Caveolin-1 (Cav-1) is a membrane protein. Recently, it has been reported that secreted Cav-1 induces angiogenesis in inflammatory microenvironment. However, it is unclear that Cav-1 regulates gingival inflammation. Therefore, we investigated the Cav-1 function to periodontal cells. Expression of Cav-1 in human periodontitis tissues was examined pathologically. Secretion of Cav-1 from human gingival fibroblasts (HGFs) or human periodontal ligament cells (HPLFs) treated with IL-1β and TNF-α was examined using Western blotting. Likewise, intracellular signals induced by Cav-1 were examined. Finally, we examined whether the secreted Cav-1 induces production of inflammatory mediators in HGFs using ELISA or qRT-PCR. Pathologically, high expression of Cav-1 was observed in human periodontitis tissues. Cav-1 secretion increased in both cultured HGFs and HPLFs treated with IL-1β and TNF-α. Cav-1 induced phosphorylation of JNK and ERK, but not Stat3 in HGFs. Furthermore, Cav-1 increased proMMP-1 and VEGF secretion in HGFs, and the VEGF secretion was statistically suppressed by JNK inhibitor SP600125, but not ERK inhibitor PD98059. ProMMP-1 secretion was suppressed statistically by both SP600125 and PD98059. In addition, Cav-1 increased significantly MMP-1, -10 and -14 mRNA expressions, whereas no increase of TIMPs mRNA was observed in HGFs treated with Cav-1. These data suggest that secreted Cav-1 derived from periodontal fibroblastic cells enhances inflammation-related several proteases and VEGF secretion in HGFs via MAPKs pathway, resulting in progression of periodontitis through induction of tissue degradation or angiogenesis.
authors: Division of Periodontics, Department of Conservative Dentistry and Oral Rehabilitation, Iwate Medical University School of Dentistry, Morioka, Iwate, Japan.
authors: Naoki
authors: N
authors: Takizawa
authors: Shunsuke
authors: S
authors: Sawada
authors: Naoyuki
authors: N
authors: Chosa
authors: Akira
authors: A
authors: Ishisaki
authors: Koji
authors: K
authors: Naruishi
mesh_terms: D000873:Anthracenes / Q000494:pharmacology; D015153:Blotting, Western; D051242:Caveolin 1 / Q000235:genetics* / Q000378:metabolism*; D002470:Cell Survival; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D005881:Gingiva / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000473:pathology; D053583:Interleukin-1beta / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D053506:Matrix Metalloproteinase 10 / Q000235:genetics / Q000378:metabolism; D053511:Matrix Metalloproteinase 14 / Q000235:genetics / Q000378:metabolism; D010513:Periodontal Ligament / Q000166:cytology / Q000378:metabolism; D010518:Periodontitis / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D000873:Anthracenes; D051242:Caveolin 1; D005419:Flavonoids; D053583:Interleukin-1beta; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C432165:pyrazolanthrone; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; C511770:MMP10 protein, human; D053506:Matrix Metalloproteinase 10; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one