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

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)

A Prolonged Nitric Oxide-Dependent, Opioid-Mediated Antinociceptive Effect of Hyperbaric Oxygen in Mice

Hyperbaric oxygen (HBO 2 ) therapy is reported to cause pain relief in several conditions of chronic pain. A single 60-minute session of HBO 2 treatment produced a prolonged antinociceptive effect in mice that persisted for 90 minutes after cessation of treatment. The HBO 2 -induced antinociception was significantly attenuated by pretreatment before HBO 2 exposure with the opioid antagonist naltrexone, the nonspecific nitric oxide synthase (NOS)-inhibitor N G -nitro- l-arginine methyl ester (L-NAME), and the selective neuronal NOS-inhibitor S-methyl- l-thiocitrulline (SMTC) but not the selective endothelial NOS-inhibitor N 5-(1-iminoethyl)- l-ornithine (L-NIO). The antinociception was also significantly reduced by central pretreatment with a rabbit antiserum against dynorphin 1-13 but not by rabbit antisera against either β-endorphin or methionine-enkephalin. The prolonged antinociceptive effect at 90 minutes after HBO 2-induced treatment was also significantly attenuated by naltrexone but not L-NAME administered 60 minutes after HBO 2 treatment but before nociceptive testing. These findings indicate that the antinociception that persists for 90 minutes after HBO 2 exposure is mediated by nitric oxide (NO) and opioid mechanisms but that the NO involvement is critical during the HBO 2 treatment and not at the time of nociceptive testing. These results are consistent with the concept that HBO 2 may induce an NO-dependent release of opioid peptide to cause a long-acting antinociceptive effect. This article presents evidence of a persistent antinociceptive effect of hyperbaric oxygen treatment that is mediated by opioid and NO mechanisms. Further elucidation of the underlying mechanism could identify molecular targets to cause a longer-acting activation of endogenous pain-modulating systems

Hyperbaric Oxygen Treatment Induces a 2-Phase Antinociceptive Response of Unusually Long Duration in Mice

Hyperbaric oxygen (HBO 2) therapy is approved by the FDA for limited clinical indications but is reported to produce pain relief in several chronic pain conditions. However, there have been no studies to explain this apparent analgesic effect of HBO 2. Research conducted in our laboratory demonstrates that 4 daily 60-minute HBO 2 treatments at 3.5 absolute atmospheres induced an unparalleled antinociceptive response that consists of 1) an early phase that lasted at least 6 hours after the HBO 2 treatment before dissipating; and 2) a late phase that emerged about 18 hours after the early phase and lasted for up to 3 weeks. The early phase was sensitive to antagonism by acutely intracerebroventricular (i.c.v.)-administered opioid antagonist naltrexone and the nitric oxide synthase (NOS)-inhibitor L-NAME. The late phase was inhibited by treatment with i.c.v. naltrexone or L-NAME during the 4 daily HBO 2 treatments but was not antagonized by either naltrexone or L-NAME following acute pretreatment 2 weeks after HBO 2 treatment. These experimental results implicate a novel mechanism that is activated by HBO 2, resulting in an antinociceptive response of unusually long duration that is of potential interest in the clinical management of pain. Hyperbaric oxygen treatment of mice can induce a 2-phase antinociceptive response of unusually long duration. Nitric oxide and opioid receptors appear to initiate or mediate both phases of the antinociceptive response. Further elucidation of the underlying mechanism may potentially identify molecular targets that cause long-lasting activation of endogenous analgesic systems