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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

View larger version (82K): [in this window] [in a new window]   Figure 1. Immunolocalization of cytokines in gingival tissue. In healthy control samples, IL-1ß (A), TNF- (B), and IL-17 (C) immunoreactive cells were less frequent (***p < 0.001) compared with cells in persons with periodontitis (D,E,F). IL-1ß, TNF-, and IL-17 immunopositive cells in persons with periodontitis vs. healthy control individuals were 1726 ± 81 vs. 344 ± 20, 1594 ± 147 vs. 411 ± 17, and 162 ± 21 vs. 26 ± 2, respectively. The inserted figures are magnified 3x from original arrowed area. Scale bar = 100 µm. The histograms demonstrate the number of IL-1ß-, TNF--, and IL-17-positive cells in controls and periodontitis.

View larger version (14K): [in this window] [in a new window]   Figure 2. Effects of IL-1ß, TNF-, and IL-17 (all 10 ng/mL for 48 hrs) on induction of proMMP-1 and MMP-3 concentration in gingival fibroblast cultures (n = 5) in vitro. proMMP-1 and especially MMP-3 were induced as a result of IL-1ß, TNF-, and IL-17 stimulation. The results are from triplicate measurements; mean ± SEM are shown. *p < 0.05, **p < 0.01, ***p < 0.001 (analyses by ANOVA).

View larger version (76K): [in this window] [in a new window]   Figure 3. Immunolocalization of pro- and active MMP-1 (A,C) and MMP-3 (B,D) in gingival tissue. The numbers of MMP-1- and MMP-3-immunoreactive cells were increased in persons with periodontitis. The number of MMP-1-immunoreactive cells was 1426 ± 96 vs. 497 ± 36 (***p < 0.001) and MMP-3-immunoreactive cells 1103 ± 95 vs. 274 ± 14 (***p < 0.001) cells/mm2 in persons with periodontitis compared with healthy controls, respectively. Scale bar = 100 µm. The histograms demonstrate the numbers of MMP-1- and MMP-3-positive cells in control individuals and persons with periodontitis.

View larger version (9K): [in this window] [in a new window]   Figure 4. Effect of IL-17 (10 ng/mL for 48 hrs) on induction of (A) IL-6 and IL-8 synthesis and release by gingival fibroblasts, and (B) IL-1ß and TNF- synthesis and release by adherent human monocyte/ macrophages in vitro. The results are from triplicate measurements, n = 5, for both non-stimulated (black bars) and stimulated cultures (white bars). Means ± SEM are shown. *p < 0.05; analysis by t tests.