Expression of caspase-3, p53 and Bcl-2 in generalized aggressive periodontitis.

BACKGROUND: Apoptosis, or programmed cell death is a form of physiological cell death. It is increased or decreased in the presence of infection, inflammation or tissue remodelling. Previous studies suggest that apoptosis is involved in the pathogenesis of inflammatory periodontal disease. The aim of the present study was to investigate the clinical features and known indicators of apoptosis (p53, Bcl-2, Caspase-3) in patients with generalized aggressive periodontitis (GAP) METHODS: Eight patients with GAP, who had sites with probing depths (PD) > 5 mm, and 10 periodontally-healthy persons were included in the study. Clinical examinations and PD were performed, and the plaque index and gingival index were recorded. Gingival tissues biopsies were obtained from active site of each patient and from healthy individuals. The expression of caspase-3, Bcl-2, and p53 was evaluated by immunohistochemistry RESULTS: There were no significant differences between GAP and control group with respect to levels of caspase-3 and p53 expression (P > 0.05). Contrary, the frequency of grade 3 expression of Bcl-2 was higher in GAP group than the control group. CONCLUSION: The higher frequency of Bcl-2 expression in GAP group indicates and delayed apoptosis can lead to increasing resident inflammatory cells in periodontal tissues and resulting in progressive periodontal destruction.

Analysis of proliferative activity in oral gingival epithelium in immunosuppressive medication induced gingival overgrowth.

BACKGROUND: Drug-induced gingival overgrowth is a frequent adverse effect associated principally with administration of the immunosuppressive drug cyclosporin A and also certain antiepileptic and antihypertensive drugs. It is characterized by a marked increase in the thickness of the epithelial layer and accumulation of excessive amounts of connective tissue. The mechanism by which the drugs cause gingival overgrowth is not yet understood. The purpose of this study was to compare proliferative activity of normal human gingiva and in cyclosporine A-induced gingival overgrowth. METHODS: Gingival samples were collected from 12 generally healthy individuals and 22 Cyclosporin A-medicated renal transplant recipients. Expression of proliferating cell nuclear antigen was evaluated in formalin-fixed, paraffin-embedded gingival samples using an immunoperoxidase technique and a monoclonal antibody for this antigen. RESULTS: There were differences between the Cyclosporin A group and control group in regard to proliferating cell nuclear antigen and epithelial thickness. In addition, the degree of stromal inflammation was higher in the Cyclosporin A group when compared with the control group. CONCLUSION: The results suggest that the increased epithelial thickness observed in Cyclosporin A-induced gingival overgrowth is associated with increased proliferative activity in keratinocytes.

Apoptosis in cyclosporin A-induced gingival overgrowth: a histological study.

BACKGROUND: Cyclosporin A (CsA) is known to induce gingival overgrowth. Apoptosis plays a critical role in the regulation of inflammation and the host immune response. The aim of this study was to investigate apoptosis in CsA-induced gingival enlargement using electron microscopy examination of keratinocytes. METHODS: Gingiva specimens were collected from 12 CsA-treated renal transplant patients with gingival overgrowth and eight healthy controls with gingivitis. Clinical findings (probing depth, gingival index, and plaque index) were compared in the two groups. Histological and ultrastructural features of the specimens were also compared, and extent of keratinocyte apoptosis was scored on a three-tier scale: 0 = no apoptotic cells; 1 = one or two apoptotic cells; 2 = more than two cells. RESULTS: There were no significant differences between groups with respect to gingiva-related clinical findings or extent of keratinocyte apoptosis. CONCLUSIONS: The results indicate that the extent of keratinocyte apoptosis in the gingiva of kidney recipients with CsA-induced gingival overgrowth is similar to that observed in inflamed gingiva of healthy individuals. Further studies on apoptosis of different cell types in the presence of CsA should clarify this agent's role in the pathogenesis of drug-induced gingival enlargement.

Effect of cyclosporin A on apoptosis and expression of p53 and bcl-2 proteins in the gingiva of renal transplant patients.

BACKGROUND: Gingival overgrowth (GO) is a common side effect of cyclosporin A (CsA) therapy, but the exact mechanism for this is unknown. Apoptosis plays an important role in the maintenance of tissue homeostasis and mediators of this process may be involved in the pathogenesis of drug-induced GO. This study compared p53 expression, bcl-2 expression, and apoptosis in gingival samples from CsA-treated renal transplant recipients to findings in controls with gingivitis. METHODS: Twenty-two kidney recipients with CsA-induced GO and 15 systemically healthy subjects with gingivitis were included in the study. The 15 systemically and periodontally healthy volunteer control group were immunohistochemically analyzed for grades of p53 and bcl-2 expression, and were processed using terminal TdT-mediated dUTP-biotin nick-end labeling (TUNEL) technique to identify and grade levels of apoptosis. RESULTS: There were no differences between the CsA group and the control group with respect to grades of p53 and bcl-2 expression (P >0.05 for both). However, the CsA group showed a lower apoptosis grade than the control group (P <0.05). None of the clinical parameters was significantly correlated with any of the immunohistochemical findings for p53 or bcl-2 (P >0.05 for all). Similarly, grade of apoptosis was not correlated with any of the clinical parameters (P >0.05). There was a significant positive correlation between serum CsA level and level of bcl-2 expression, but serum CsA was not significantly correlated with level of apoptosis or level of p53 expression. CONCLUSION: The results indicate that the pathogenesis of CsA-induced GO might involve inhibition of apoptosis, and overexpression of bcl-2 in the setting of high serum CsA.

Immunohistochemical study of cyclosporin-induced gingival overgrowth in renal transplant recipients.

BACKGROUND: Cyclosporin A (CsA) is an immunosuppressant widely used to treat transplant patients and various systemic diseases with immunological components. Gingival overgrowth (GO) is a common side effect of CsA administration; however, the pathogenesis of drug-induced GO is poorly understood. The aim of this study was to evaluate the expression of Ki-67, activation molecules (CD71, CD98), leukocytes activation antigens (CD45, CD45RA, CD50, CD11a, CD162, CD227, CD231), neurothelin (CD147), and novel endothelial cell antigens (B-F45, SCF87, B-D46, B-C44, VJ1/6) in gingival tissue in renal transplant recipients treated with CsA. METHODS: Tissues from 15 renal transplant patients with significant GO and 10 systemically healthy control subjects with gingivitis were studied. Frozen-section biopsies were stained with monoclonal antibodies specific for the above-mentioned antigens using an indirect immunoperoxidase technique. RESULTS: Comparison of the CsA-treated and control groups revealed no significant differences with respect to expression of Ki-67; CD50; activation molecules; neurothelin; or novel endothelial cell antigens B-D46, B-C44, and VJ1/6. However, expression patterns of CD45, CD45RA, CD11a, CD162, CD227, CD231, B-F45, and SCF87 were significantly different in CsA and control groups. CONCLUSION: Leukocyte activation antigens play an important role in CsA-induced gingival overgrowth.