| 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
|
| リソース情報 |
| ヒト・動物細胞 |
Ca9-22(RCB1976) |
