論文 - 詳細
| RRC ID | 45489 |
|---|---|
| 著者 | Goto H, Ishihara Y, Kikuchi T, Izawa A, Ozeki N, Okabe E, Kamiya Y, Ozawa Y, Mizutani H, Yamamoto G, Mogi M, Nakata K, Maeda H, Noguchi T, Mitani A. |
| タイトル | Interleukin-1 Receptor Antagonist Has a Novel Function in the Regulation of Matrix Metalloproteinase-13 Expression. |
| ジャーナル | PLoS One |
| Abstract |
Interleukin-1 receptor antagonist (IL-1Ra) is an IL-1 family member, which binds to IL-1 receptors but does not induce any intracellular signaling. We addressed whether IL-1Ra has a novel function in regulation of the extracellular matrix or adhesion molecules. Polymerase chain reaction array analysis demonstrated a ~5-fold increase in matrix metalloproteinase 13 (MMP-13) mRNA expression of IL-1Ra siRNA-transfected Ca9-22 human oral squamous epithelial carcinoma cells compared with the control. In fact, MMP-13 mRNA and protein expression as well as its activity in IL-1Ra siRNA-transfected Ca9-22 cell lines were significantly higher than those in the control. IL-1Ra siRNA treatment resulted in strong elevation of MMP-13 expression, whereas addition of rhIL-1Ra (40 ng/ml) suppressed MMP-13 expression, suggesting that IL-1Ra had a specific effect on MMP-13 induction. IL-1Ra siRNA could potently suppress IL-1α. No significant difference was found between the MMP-13 mRNA expression of IL-1Ra siRNA-transfected cells and those treated with anti-IL-1α or anti-IL-1β antibodies. These results suggested that continuous supply of IL-1 had no effect on the induction of MMP-13 by IL-1Ra siRNA. Histopathological investigation of MMP-13 in periodontal tissue showed specific localization in the junctional epithelial cells of IL-1Ra knockout (KO) mice. Furthermore, infection with Aggregatibacter actinomycetemcomitans to establish an experimental periodontitis model resulted in predominant localization of MMP-13 along apical junctional epithelial cells. Laminin-5, which is degraded by MMP-13, was found in the internal basal lamina of wild-type mice, whereas the internal basal lamina of IL-1Ra KO mice did not show obvious laminin-5 localization. In particular, laminin-5 localization almost disappeared in the internal basal lamina of IL-1Ra KO mice infected with A. actinomycetemcomitans, suggesting that the suppression of IL-1Ra resulted in strong induction of MMP-13 that degraded laminin-5. In conclusion, IL-1Ra is associated with MMP-13 expression and has a novel function in such regulation without interference of the IL-1 signaling cascade. |
| 巻・号 | 10(10) |
| ページ | e0140942 |
| 公開日 | 2015-1-1 |
| DOI | 10.1371/journal.pone.0140942 |
| PII | PONE-D-15-24138 |
| PMID | 26474296 |
| PMC | PMC4608771 |
| MeSH | Aggregatibacter actinomycetemcomitans Animals Cell Adhesion Molecules / genetics Cell Adhesion Molecules / metabolism Cell Line, Tumor Gene Expression Regulation, Enzymologic / physiology* Humans Interleukin 1 Receptor Antagonist Protein / genetics Interleukin 1 Receptor Antagonist Protein / metabolism* Interleukin-1alpha / biosynthesis Interleukin-1alpha / genetics Matrix Metalloproteinase 13 / biosynthesis* Matrix Metalloproteinase 13 / genetics Mice Mice, Knockout Pasteurellaceae Infections / genetics Pasteurellaceae Infections / metabolism Proteolysis* RNA, Small Interfering / genetics Signal Transduction / physiology* |
| IF | 2.74 |
| 引用数 | 5 |
| WOS 分野 | DENTISTRY, ORAL SURGERY & MEDICINE |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | Ca9-22(RCB1976) |