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MMPs, IL-1, and TNF are Regulated by IL-17 in Periodontitis

¹ Department of Medicine/Invärtes medicin, Helsinki University Central Hospital, Helsinki, Finland;
² Institute of Biomedicine/Anatomy, University of Helsinki, Finland;
³ Medico-social Centre, Dental Clinic, Bogazici University, Istanbul, Turkey;
⁴ ORTON Orthopaedic Hospital of the Invalid Foundation, Helsinki, Finland;
⁵ Department of Periodontology, Faculty of Dentistry, Ankara University, Turkey;
⁶ Institute of Dentistry, University of Helsinki, Dept. of Oral and Maxillofacial Diseases, Helsinki University Central Hospital, Finland;
⁷ COXA Hospital for Joint Replacement, Tampere, Finland

^* corresponding author, yrjo.konttinen{at}helsinki.fi, Biomedicum Helsinki, PO Box 700 (Haartmaninkatu 8), FI-00029 HUS-Finland

Periodontitis is characterized by periodontal tissue destruction. Since interleukin-17 (IL-17) has been reported to up-regulate IL-1ß and tumor necrosis factor-alpha (TNF-), it was hypothesized that it is increased in periodontitis and up-regulates these cytokines and tissue-destructive matrix metalloproteinases (MMP) in local migrant and resident cells. Immunocytochemistry disclosed elevated IL-1ß, TNF-, and IL-17 levels in periodontitis. These cytokines induced proMMP-1 and especially MMP-3 in gingival fibroblasts, whereas MMP-8 and MMP-9 were not induced. IL-17 was less potent as a direct MMP inducer than IL-1ß and TNF-, but it induced IL-1ß and TNF- production from macrophages, and IL-6 and IL-8 from gingival fibroblasts. In accordance with these findings, immunocytochemistry disclosed that MMP-1 and MMP-3 were increased in periodontitis. Gingival fibroblasts may play an important role in tissue destruction in periodontitis via cytokine-inducible MMP-1 and MMP-3 production, in which IL-17 plays a role as a key regulatory cytokine.

KEY WORDS: IL-1ß • TNF- • IL-17 • MMP • periodontitis

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