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Interleukin-12-mediated expression of matrix metalloproteinases in human periodontal ligament fibroblasts involves in NF-κB activation.
| Content Provider | Europe PMC |
|---|---|
| Author | Miao, Li Zhan, Shujun Liu, Jiyan |
| Copyright Year | 2017 |
| Abstract | Interleukin-12 (IL-12) is a proinflammatory cytokine, and its increased level correlates with the severity of periodontitis. However, its role in the pathogenesis of tooth periapical lesions is controversial and has not been completely clarified. The present study aimed to investigate whether IL-12 affects the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in human periodontal ligament fibroblasts (hPDLFs). After treatment with IL-12 for different times, real-time PCR and Western blotting were used to determine the mRNA and protein levels of MMP-1, MMP-2, MMP-3, MMP-9, MMP-13, TIMP-1, and TIMP-2, respectively. ELISA was applied to measure MMPs and TIMPs secretion production. The results indicated that IL-12 significantly increased the mRNA and protein expression levels of MMP-1, MMP-3, and MMP-13, but down-regulated MMP-2 and MMP-9 mRNA and protein expression in the hPDLFs. Furthermore, IL-12 (10 ng/ml) enhanced the secreted protein production of MMP-1, MMP-3, and MMP-13, and conversely lowered MMP-2 and MMP-9 secretion levels. However, IL-12 treatment did not exert a significant effect on the mRNA and protein levels of TIMP-1 and TIMP-2 and their secreted production. Additionally, IL-12 increased the phosphorylated levels of IκBα and nuclear factor-κB P65 (NF-κB P65), and promoted NF-κB P65 subunit nuclear translocation. Pretreatment with NF-κB inhibitor not only attenuated IL-12-induced IκBα and NF-κB P65 phosphorylation and inhibited NF-κB P65 subunit into nucleus, but also antagonized IL-12-mediated MMP-1, MMP-2, MMP-3, MMP-9, and MMP-13 expression in the hPDLFs. These findings indicate that NF-κB-dependent activation is possibly indispensable for IL-12-mediated MMP expression in hPDLFs. |
| Page Count | 10 |
| ISSN | 01448463 |
| Volume Number | 37 |
| PubMed Central reference number | PMC5696454 |
| Issue Number | 6 |
| PubMed reference number | 29054963 |
| Journal | Bioscience Reports [Biosci. Rep] |
| e-ISSN | 15734935 |
| DOI | 10.1042/BSR20170973 |
| Language | English |
| Publisher | Portland Press Ltd. |
| Publisher Date | 2017-11-21 |
| Access Restriction | Open |
| Rights License | This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY). © 2017 The Author(s). |
| Subject Keyword | Interleukin-12 Matrix metalloproteinases NF-kappaB Periodontal ligament Periodontitis |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Molecular Biology Biochemistry Biophysics |
