The effect of IL-17 on the production of proinflammatory cytokines and matrix metalloproteinase-1 by human periodontal ligament fibroblasts

• Published in: Orthodontics & craniofacial research 2014-02, Vol.17 (1), p.60-68
• Main Authors: Shibata, M., Shintaku, Y., Matsuzaki, K., Uematsu, S.
• Format: Article
• Language: English
• Subjects: Cell Culture Techniques; Cells, Cultured; Cytokines - drug effects; Dentistry; Fibroblasts - drug effects; Fibroblasts - immunology; Humans; IL-17; IL-1β; IL-6; Inflammation Mediators - analysis; Interleukin-17 - immunology; Interleukin-17 - pharmacology; Interleukin-1beta - analysis; Interleukin-1beta - pharmacology; Interleukin-6 - analysis; Interleukin-6 - pharmacology; Matrix Metalloproteinase 1 - analysis; Matrix Metalloproteinase 1 - drug effects; matrix metalloproteinase-1; Periodontal Ligament - cytology; Periodontal Ligament - drug effects; periodontal ligament cells; Receptors, Interleukin-6 - analysis; Receptors, Interleukin-6 - immunology; Time Factors
• ISSN: 1601-6335; 1601-6343
• DOI: 10.1111/ocr.12033

Structured Objectives To investigate the effects of IL‐17 on IL‐6, IL‐1β, and matrix metalloproteinase (MMP‐1) production, and to compare the MMP‐1 production between the individual and combined effects of IL‐1β and IL‐6 in human periodontal ligament fibroblasts (HPDLF). Materials and Methods Human periodontal ligament fibroblasts were cultured with IL‐17 for 0.5, 1, 4, 24, 48, and 72 h, and were cultured with IL‐1β, IL‐6/sIL‐6R, or a combination of IL‐1β and IL‐6/sIL‐6R for 24 h. To measure the mRNA levels of IL‐6, IL‐1β, and MMP‐1, total RNA was extracted from the cultured HPDLF, and a real‐time PCR analysis was performed. The protein levels of IL‐6, IL‐1β, and MMP‐1 in supernatants were measured using enzyme‐linked immunosorbent assays (ELISAs). Results IL‐17 significantly increased the expression of IL‐6 and MMP‐1 mRNA and protein, while IL‐17 transiently increased the expression of IL‐1β mRNA. The combination of IL‐1β and IL‐6/sIL‐6R induced significantly higher levels of MMP‐1 protein than IL‐1β alone. Conclusions IL‐17 upregulated the production of IL‐6 and MMP‐1 sequentially in HPDLF. IL‐6/sIL‐6R may enhance the effects of IL‐1β on MMP‐1 production. The present results suggest that IL‐17 induces MMP‐1 production not only directly, but also indirectly by promoting IL‐6 production, thus resulting in the degradation of collagens in the PDL.