Evaluation of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 levels in gingival fibroblasts of cyclosporin A-treated patients

WOS: 000179500900004PubMed ID: 12479630Background: Cyclosporin A (CsA) is a potent immunosuppressant used to prevent organ transplant rejection and to treat various autoimmune diseases. CsA-induced gingival overgrowth (CsA GO) is the most widely seen side effect of this drug; its pathogenesis is not completely understood. The aim of this study was to identify and compare matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels in gingival fibroblast cultures of tissues derived from renal transplant patients receiving CsA and exhibiting gingival overgrowth and from periodontally healthy control subjects. Methods: Gingival overgrowth samples were obtained from patients undergoing therapy with CsA, and control tissues were obtained from systemically healthy donors. Gingival fibroblasts were grown using explant cultures. Three different study groups were identified: 1) CsA GO fibroblast culture; 2) CsA-treated healthy gingival fibroblast culture (H+CsA); and 3) healthy gingival fibroblast culture (H). The levels of MMP-1 and TIMP-1 in these groups of gingival fibroblasts were analyzed by enzyme-linked immunoabsorbent assay (ELISA). Results: The levels of TIMP-1 were significantly lower in CsA GO than H (P <0.05). There was no statistically significant difference in the levels of MMP-1 between H and CsA GO (P <0.505). The ratio of MMP-1 to TIMP-1 was significantly higher in CsA GO than H (P <0.05). Conclusions: The results of this study indicate that CsA therapy does not have a significant effect on MMP-1 levels. However, low TIMP-1 levels can be an important factor in the pathogenesis of CsA GO, since the balance between MMP-1 and TIMP-1 levels was changed by CsA

Effects of low-dose doxycycline and bisphosphonate clodronate on alveolar bone loss and gingival levels of matrix metalloproteinase-9 and interleukin-1 ß in rats with diabetes: A histomorphometric and immunohistochemical study

Background: Bisphosphonates (BPs) and low-dose doxycycline (LDD) have been shown to inhibit bone resorption and to improve the levels of proinflammatory mediators and destructive enzymes in gingival tissues, respectively. The purpose of this study is to evaluate the effect of mono and combined BP clodronate and LDD therapies in reducing gingival levels of matrix metalloproteinase-9 (MMP-9), interleukin-1ß (IL-1ß), and alveolar bone loss in rats with diabetes. Methods: Fifty adult Wistar rats were divided into five study groups as follows: 1) group 1 = diabetes control; 2) group 2 = diabetes + periodontitis; 3) group 3 = diabetes + periodontitis + LDD; 4) group 4 = diabetes + periodontitis + clodronate; and 5) group 5 = diabetes + periodontitis + LDD + clodronate. LDD and clodronate were given as a single agent or as combination therapy during the 7 days of the post-experimental periodontitis period. On day 7, the rats were sacrificed, the mobility of the tooth was recorded, and block biopsies were removed. The gingival tissues were analyzed histologically and immunohistochemically for expression of MMP-9 and IL-1ß. Alveolar bone loss was evaluated morphometrically under a light microscope. Data analysis was performed statistically by Kruskal-Wallis and post hoc Tukey and Spearman correlation tests. Results: Alveolar bone loss was significantly greater in groups 2 through 5 than group 1 (P 0.05). Animals with periodontitis (group 2) expressed significantly higher levels of MMP-9 and IL-1ß compared with those without periodontitis (group 1) (P <0.05). MMP-9 expression was significantly lower in group 3 than groups 1, 2, and 5 (P <0.05). IL-1ß expression was significantly lower in the groups 1, 3, 4, and 5 than 2 (P <0.01) but was not significantly different among groups 1, 3, 4, and 5. Positive correlations were found between alveolar bone loss and density of inflammation (? = 0.319, P = 0.021) and between MMP-9 and IL-1ß (? = 0.418, P = 0.002), respectively. Conclusion: Our findings suggest that ligature-induced periodontitis in animals with diabetes results in significantly higher levels of MMP-9 and IL-1ß expression in gingiva. The use of mono and combined clodronate and LDD administrations may significantly reduce levels of MMP-9 and IL-1ß expression. However, drug administration did not affect alveolar bone levels during the study period

Gingival crevicular fluid levels of monocyte chemoattractant protein-1 and tumor necrosis factor-alpha in patients with chronic and aggressive periodontitis

Background: Monocyte chemoattractant protein-1 (MCP-1) is a well-known chemotactic cytokine that regulates mononuclear inflammatory cell recruitment. This recruitment has particular importance in the oral cavity because inflammatory cells will be challenged with periodontopathogenic bacteria during infections. Tumor necrosis factor-alpha (TNF-alpha) is a cytokine that induces bone resorption by stimulating proliferation and differentiation of osteoclasts' progenitors and also stimulates MCP-1 expression. The aims of this study were to investigate the presence of MCP-1 in gingival crevicular fluid (GCF) samples from patients with chronic periodontitis (CP) and aggressive periodontitis (AgP) and to examine the possible correlations between the GCF levels of MCP-1 and TNF-alpha

Evaluation of gingival crevicular fluid levels of tissue plasminogen activator, plasminogen activator inhibitor 2, matrix metalloproteinase-3 and interleukin 1-beta in patients with different periodontal diseases

WOS: 000347467600006PubMed: 24690077ObjectivesThe purpose of this study was to evaluate the gingival crevicular fluid levels of interleukin-1beta (IL-1), matrix metalloproteinases-3 (MMP-3), tissue type plasminogen activator (t-PA) and plasminogen activator inhibitor 2 (PAI-2) in patients with chronic periodontitis, aggressive periodontitis (AgP) and healthy individuals (controls). Material and MethodsSystemically healthy (21 chronic periodontitis, 23 AgP and 20 controls) subjects were included in this study. Plaque index, gingival index, probing pocket depth and clinical attachment level were recorded and gingival crevicular fluid samples were collected. Assays for IL-1, MMP-3, t-PA and PAI-2 levels in gingival crevicular fluid were carried out by an enzyme-linked immunosorbent assay. The one-sample Kolmogorov-Smirnov test, Mann-Whitney U test and Spearman correlation coefficient were used for data analyses. ResultsGingival crevicular fluid levels of t-PA and IL-1 were significantly higher in chronic periodontitis and AgP groups than in the control group (p<0.001). MMP-3 levels in gingival crevicular fluid were detected as significantly higher in the chronic periodontitis and AgP groups compared with the control group (p<0.05). The t-PA/PAI-2 rate of patients with chronic periodontitis and AgP were significantly higher than the control group (p<0.05). The positive correlations were found among the PAI-2, t-PA, IL-1 and MMP-3 levels in gingival crevicular fluid. The volume of the gingival crevicular fluid correlated with all of the clinical parameters (p<0.001). There were positive correlations between the gingival crevicular fluid levels of PAI-2 and the probing pocket depth and between gingival crevicular fluid levels of PAI-2 and the clinical attachment level (p<0.01). Similarly, significant correlations were found between t-PA levels and probing pocket depth and between t-PA levels and clinical attachment level measurements (p<0.001). ConclusionThe present data showed that gingival crevicular fluid levels of IL-1 , MMP-3 and t-PA increased in periodontal disease regardless of the periodontitis type and played a part in tissue destruction.Scientific Research Foundation of Gazi UniversityGazi University [03/2006-19]; Gazi University research grantGazi University [03/2006-19]This research was supported by Scientific Research Foundation of Gazi University (no. 03/2006-19). The authors declare that they have no conflicts of interest related to this study. This study was financially supported by a Gazi University research grant (no. 03/2006-19)