Regulation of matrix metalloproteinases, tissue inhibitor of matrix metalloproteinase-1, and extracellular metalloproteinase inducer by interleukin-17 in human periodontal ligament fibroblasts

Abstract

Introduction: Under physiological conditions, matrix metalloproteinases (MMPs) are involved in the turnover of periapical tissue, and their activity is tightly regulated by tissue inhibitors of metalloproteinases (TIMPs). Disturbances in the balance between MMPs and TIMPs may result in excessive tissue destruction. In addition, the extracellular metalloproteinase inducer (EMMPRIN) capable of inducing MMPs may also play a role in the pathologic processes. This study aimed to investigate the effects of interleukin (IL)-17 on the mRNA expression and protein production of MMP-1, MMP-2, MMP-9, MMP-13, TIMP-1, and EMMPRIN through human periodontal ligament cells.

Methods: The cells were stimulated with IL-17 (1, 10, and 50 ng/mL) for different time periods. The mRNA levels of MMP-1, MMP-2, MMP-9, MMP-13, TIMP-1, and EMMPRIN were evaluated via quantitative real-time polymerase chain reaction analysis, whereas the protein secretion into the culture medium was assessed via enzyme-linked immunosorbent assay and zymography analysis.

Results: IL-17 significantly up-regulated MMP-1 and MMP-13 mRNA expression but down-regulated MMP-2, MMP-9, and TIMP-1 mRNA expression. Furthermore, IL-17 (50 ng/mL) increased the secreted protein level of MMP-1 and MMP-13 and conversely reduced the level of MMP-2, MMP-9, and TIMP-1. However, IL-17 exerted no effect on EMMPRIN mRNA or protein secretion.

Conclusions: This study first reported the ability of IL-17 to regulate MMP and TIMP-1 production through human periodontal ligament cells, a phenomenon that may contribute to periapical tissue destruction.