IL‑18 promotes the secretion of matrix metalloproteinases in human periodontal ligament fibroblasts by activating NF‑κB signaling

Wang,Fang; Guan,Min; Wei,Liting; Yan,Hui

doi:10.3892/mmr.2018.9697

IL‑18 promotes the secretion of matrix metalloproteinases in human periodontal ligament fibroblasts by activating NF‑κB signaling

Authors:
- Fang Wang
- Min Guan
- Liting Wei
- Hui Yan
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Affiliations: Department of Stomatology, Tianjin Nankai Hospital, Tianjin 300010, P.R. China, Department of Stomatology, Inner Mongolia Autonomous Region People's Hospital, Hohhot, Inner Mongolia 010017, P.R. China, Department of Stomatology, Changchun Stomatological Hospital, Changchun, Jilin 130022, P.R. China
Published online on: November 26, 2018 https://doi.org/10.3892/mmr.2018.9697
Pages: 703-710

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Abstract

Chronic periodontitis is the most common periodontal disease and is characterized by progressive degeneration of periodontal tissue. Periodontal‑specific pathogens can induce the expression of various inflammatory cytokines in periodontal ligament cells and their secretion into peripheral blood. These inflammatory cytokines have an important role in the occurrence and development of chronic periodontitis. ELISA was used to detect the expression of interleukin‑18 (IL‑18) protein in the serum and saliva of 30 healthy volunteers and 30 patients with chronic periodontitis. The clinical parameters that were assessed included plaque index, gingival index, periodontal probing depth and attachment loss. The effect of IL‑18 on the viability of human periodontal ligament fibroblasts (hPDLFs) was examined using a Cell Counting Kit‑8 assay. The effects of IL‑18 on mRNA expression and secretion of matrix metalloproteinase (MMP)1, MMP2, MMP3 and MMP9 in hPDLFs were detected by reverse transcription‑quantitative polymerase chain reaction and ELISA, respectively. The effect of IL‑18 on the phosphorylation of nuclear factor‑κB (NF‑κB) p65 protein and the protein expression of MMP1, MMP2, MMP3 and MMP9 in hPDLF cells was detected by western blotting. The expression level of IL‑18 in the serum of patients with chronic periodontitis was significantly higher than that of healthy volunteers, and the expression level of IL‑18 in saliva was positively correlated with the periodontal destruction. However, IL‑18 did not have a significant effect on the viability ability of hPDLFs. IL‑18 promoted phosphorylation of NF‑κB p65 protein in hPDLF, and increased the mRNA expression and protein secretion of MMP1, MMP2, MMP3 and MMP9. These findings indicate that IL‑18 promotes the secretion of MMP1, MMP2, MMP3, and MMP9 in hPDLFs by activating the NF‑κB signaling pathway, which has a key role in the development of chronic periodontitis. Therefore, targeting IL‑18 may be a new research direction for the treatment of chronic periodontal disease.

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