Interleukin-12-mediated expression of matrix metalloproteinases in human periodontal ligament fibroblasts involves in NF-κB activation
Open Access
- 21 November 2017
- journal article
- Published by Portland Press Ltd. in Bioscience Reports
- Vol. 37 (6)
- https://doi.org/10.1042/bsr20170973
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.This publication has 47 references indexed in Scilit:
- TLR4-mediated IL-12 production enhances IFN-γ and IL-1β production, which inhibits TGF-β production and promotes antibody-induced joint inflammationArthritis Research & Therapy, 2012
- Estimation of matrix metalloproteinase‑3 levels in gingival crevicular fluid in periodontal disease, health and after scaling and root planingJournal of Indian Society of Periodontology, 2012
- Opposing Roles for CXCR3 Signaling in Central Nervous System Versus Ocular Inflammation Mediated by the Astrocyte-Targeted Production of IL-12The American Journal of Pathology, 2011
- IL-17R activation of human periodontal ligament fibroblasts induces IL-23 p19 production: Differential involvement of NF-κB versus JNK/AP-1 pathwaysMolecular Immunology, 2011
- Prevalence and simultaneous occurrence of periodontitis and dental cariesJournal of Clinical Periodontology, 2010
- Matrix Metalloproteinase Expression in Teeth with Apical Periodontitis Is Differentially Modulated by the Modality of Root Canal TreatmentJournal of Endodontics, 2010
- A Controversial Role for IL-12 in Immune Response and Bone Resorption at Apical Periodontal SitesJournal of Immunology Research, 2010
- IL-12 stimulates the osteoclast inhibitory peptide-1 (OIP-1/hSca) gene expression in CD4+ T cellsJournal of Cellular Biochemistry, 2009
- Down‐regulation of interleukin‐1α‐induced matrix metalloproteinase‐13 expression via EP1 receptors by prostaglandin E2 in human periodontal ligament cellsOral Microbiology and Immunology, 2004
- In vitro expression of matrix metalloproteinase-1, tissue inhibitor of metalloproteinase-1 and transforming growth factor- 1 in human periodontal ligament fibroblastsEuropean Journal of Orthodontics, 2004