Plasminogen activators and plasminogen activator inhibitors in gingival crevicular fluid of cyclosporin A-treated patients

BACKGROUND: The plasminogen activator (PA) system plays many roles in the inflammatory process and tissue remodelling and repair and is considered to play a significant role in periodontal tissue destruction and healing. The aim of this study was to evaluate the role of the PA system in cyclosporin A (CsA)-induced gingival overgrowth in renal transplant patients. METHODS: Eighteen renal transplant patients exhibiting moderate to severe CsA-induced gingival overgrowth, 10 other renal transplant patients receiving CsA therapy but showing no sign of CsA-induced gingival overgrowth (CsA-H), 16 chronic gingivitis patients (CG) and 16 systemically and periodontally healthy control subjects (H) were included in the study. Gingival crevicular fluid (GCF) samples were obtained from four randomly selected sites in each subject with the exception of the CsA-induced gingival overgrowth group, where four GCF samples were harvested from sites with severe overgrowth (CsA GO+) and from four sites without any gingival overgrowth (CsA GO-). The GCF levels of albumin, tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), plasminogen activator inhibitor 1 (PAI-1) and plasminogen activator inhibitor 2 (PAI-2) were analysed by enzyme-linked immunosorbent assay. The results were tested for statistical differences. RESULTS: In CsA GO+ sites t-PA levels were significantly elevated in comparison with gingivitis and healthy sites, while PAI-2 levels in these sites showed statistically significant differences only with CsA-H and gingivitis sites (p<0.05). The levels of t-PA and PAI-2 were significantly higher in CsA GO- sites compared with those of CsA-H, gingivitis and healthy sites (p<0.05). The levels of u-PA and PAI-1 failed to show significant differences between the study groups. CONCLUSIONS: The findings of the present study indicate alterations in GCF t-PA and PAI-2 levels in CsA-induced gingival overgrowth and might suggest involvement of the plasminogen activating system in the pathogenesis of this side-effect of CsA therapy. However, to what extent these molecules contribute to the pathogenesis of CsA-induced gingival overgrowth remains to be determined.     

Evaluation of p53, bcl-2, and interleukin-15 levels in gingival crevicular fluid of cyclosporin A-treated patients

BACKGROUND: Apoptosis plays an important role in the maintenance of tissue homeostasis. Considering that apoptosis mediators may play a role in the pathogenesis of drug-induced gingival overgrowth, this study was conducted to evaluate p53, bcl-2, and interleukin-15 (IL-15) levels in gingival crevicular fluid (GCF) of cyclosporin A (CsA)-treated patients. METHODS: Twenty renal transplant patients exhibiting CsA-induced gingival overgrowth and 15 systemically healthy gingivitis patients were included in the study; 15 systemically and periodontally healthy volunteer subjects served as the healthy control group. GCF samples were obtained from one interdental site with gingival overgrowth (GO+) and one site without (GO-) from each CsA-treated patient; hyperplasia index, probing depth, papilla bleeding index, and plaque presence were recorded. One site from each gingivitis patient and healthy control was selected, GCF samples were obtained, and the same clinical parameters were recorded. GCF p53, bcl-2, and IL-15 levels were analyzed by enzyme-linked immunosorbent assay. The results were tested statistically. RESULTS: p53 and bcl-2 levels were below the minimum detectable level in all GCF samples analyzed. CsA GO+ and CsA GO- sites, as well as gingivitis sites, exhibited significantly higher GCF levels of IL-15 compared to healthy controls (P<0.05). The difference between CsA GO+ sites and gingivitis sites was not statistically significant, although the total amount of IL-15 in CsA GO+ sites was lower than gingivitis sites (P>0.05). The total amount of IL-15 in CsA GO- sites was significantly lower than gingivitis sites (P<0.05). No significant correlation was found between the clinical parameters and GCF IL-15 levels (P>0.05). CONCLUSIONS: The pathogenesis of CsA-induced gingival overgrowth is multifactorial. The findings of the present study indicate that IL-15 may play a role in the pathogenesis of CsA-induced gingival overgrowth due to its interactions with CsA and its role in apoptosis and inflammation.     

Gingival tissue proteoglycan and chondroitin-4-sulphate levels in cyclosporin A-induced gingival overgrowth and the effects of initial periodontal treatment

OBJECTIVES: Cyclosporin A (CsA) is a potent immunosuppressive drug used in organ transplant patients to prevent graft rejection. CsA-induced gingival overgrowth is one of the side effects of this drug and its pathogenesis is still unclear. The present study was planned to comparatively analyse total proteoglycan (PG) and chondroitin-4-sulphate (C4S) levels in CsA-induced overgrown gingival tissue samples obtained before and after initial periodontal treatment and to compare these findings with the situation in healthy gingiva. MATERIAL AND METHODS: Gingival tissue samples were obtained from nine patients with CsA-induced gingival overgrowth before and 4 weeks after initial periodontal treatment including oral hygiene instruction and scaling and also from 10 healthy control subjects. Total PG and C4S levels were determined by biochemical techniques. PG levels were analysed using modified Bitter and Muir method. C4S assay was carried out using chondroitin sulphate lyase AC and chondroitin-6 sulphate sulphohydrolase enzymes. The results were tested statistically using non-parametric tests. RESULTS: All clinical measurements in the CsA-induced gingival overgrowth group demonstrated significant reductions 4 weeks after initial periodontal treatment (p<0.05). There was no significant difference between the levels of baseline total PG in CsA-induced gingival overgrowth and healthy control groups (p>0.05). The gingival tissue levels of PG in CsA-induced gingival overgrowth group decreased significantly 4 weeks after treatment (p=0.043). Gingival tissue C4S levels in the overgrowth group were significantly higher than the healthy control group at baseline (p=0.000). C4S levels of the overgrowth group were significantly reduced after treatment (p=0.033), but these levels were still significantly higher than the healthy control group (p=0.000). CONCLUSION: The observed prominent increase in gingival tissue C4S levels may be interpreted as a sign of an increase in C4S synthesis in CsA-induced gingival overgrowth. Furthermore, remission of clinical inflammation by means of initial periodontal treatment had a positive effect on tissue levels of these extracellular matrix molecules.     

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.     

Toll like receptor 4 and membrane-bound CD14 expressions in gingivitis, periodontitis and CsA-induced gingival overgrowth

Objective

Immune cell recognition of lipopolysaccharides via CD14 and Toll-like receptor 4 (TLR4) complexes plays a crucial role in linking innate and adaptive immune responses. This study was aimed to investigate the expression of TLR4 and membrane-bound CD14 (mCD14) in the gingival tissues of patients with gingivitis, periodontitis and CsA-induced gingival overgrowth.

Design

Gingival tissues were obtained from 10 renal transplant patients receiving cyclosporine-A (CsA) and having gingival overgrowth (GO), 10 patients with chronic periodontitis, 10 generalized aggressive periodontitis, 10 gingivitis and 10 healthy subjects. Immunohistochemistry was performed in order to determine the localization of TLR4 and mCD14 in tissue specimens.

Results

TLR4 and mCD14 expressions were detected in all tissues including healthy gingival biopsies. TLR4 and mCD14 positive cells were predominantly confined to the epithelium–connective tissue interface area, and were highly expressed in the basal cell layer of patients with CsA GO and chronic periodontitis, compared to healthy group (P < 0.05).

Conclusion

The present study suggests that TLR4 and mCD14 protein expressions may be interrelated and appear to be associated with periodontal disease. CsA usage seemed not to affect TLR4 and mCD14 expressions in CsA induced GO tissues.     

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.     

Evaluation of transforming growth factor-beta 1 level in crevicular fluid of cyclosporin A-treated patients

BACKGROUND: The aim of the present study was to investigate the level of transforming growth factor-beta 1 (TGF-beta 1) in gingival crevicular fluid (GCF) samples of cyclosporin A (CsA)-treated patients and to compare the results with control groups. METHODS: Fourteen renal transplant patients exhibiting severe CsA-induced gingival overgrowth, 10 patients with chronic gingivitis, and 10 subjects with clinically healthy periodontium were included in the study. In CsA-treated patients, GCF samples were harvested from sites exhibiting gingival overgrowth (CsA GO+) and sites not exhibiting gingival overgrowth (CsA GO-). The TGF-beta 1 levels in a total of 96 GCF samples from the 34 participants were analyzed by enzyme-linked immunosorbent assay. The results were expressed in terms of total amount (pg/2 sites) and concentration (ng/ml). RESULTS: TGF-beta 1 total amounts in CsA GO+ and CsA GO- sites were similar and significantly higher than that of healthy sites (P < 0.02 and P < 0.01, respectively). The total amount of TGF-beta 1 was also higher in gingivitis sites compared to the healthy sites, but the difference was not statistically significant (P > 0.05). CsA GO+ and CsA GO- sites exhibited higher total amount and concentration of TGF-beta 1 than that of gingivitis sites, but the differences were insignificant (P > 0.05). CONCLUSIONS: The results of the present study support the theory that CsA increases the synthesis of TGF-beta 1 in GCF. However, since the difference between CsA GO+ and CsA GO- sites was not statistically significant, it seems unlikely that GCF TGF-beta 1 level is the sole factor responsible for the CsA-induced gingival overgrowth. Complex interactions between various mediators of inflammation and tissue modeling are possibly involved in the pathogenic mechanisms of this side effect.     

Non-surgical periodontal treatment of cyclosporin A-induced gingival overgrowth: immunohistochemical results

Aim:  The present study was planned to analyze the effects of a 12-month non-surgical periodontal treatment on histologic and immunohistochemical features of cyclosporin A (CsA)-induced gingival overgrowth (GO).
Materials and methods:  Gingival samples were collected from 21 liver transplant subjects exhibiting CsA-induced GO prior to, and 12 months after non-surgical periodontal therapy including oral hygiene instructions, scaling and 2-month recall appointments, and also from 18 healthy control subjects. Gingival biopsy specimens were stained with hematoxylin–eosin and monoclonal antibodies for vimentin, CD3 (T-lymphocytes), CD20 (B-lymphocytes), CD34 (endothelium) and Ki-67 (fibroblasts proliferation rate), using a streptavidin-biotin-peroxidase complex method.
Results:  Total inflammatory cells, gingival vessels and fibroblast proliferation rate demonstrated significant reduction after non-surgical periodontal treatment ( P  < 0.0001) in overgrown gingiva, while B- and T-lymphocytes remained nearly unchanged ( P  = 0.61 and 0.33, respectively). At the 12-month evaluation no significant differences were found when comparing the gingival biopsies from CsA-treated patients and those from healthy controls ( P  > 0.05).
Conclusions:  Control of clinical inflammation by means of non-surgical periodontal treatment results both in lowering of inflammatory infiltrate and in changes in connective tissue composition. Thus, plaque-induced inflammation would seem to modulate the drug-gingival tissue interaction.
Clinical relevance:  A strict plaque control program play a pivotal role in the management of transplant patients exhibiting cyclosporin A-GO.     

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

BACKGROUND: 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.     

Relationship between IL-1A polymorphisms and gingival overgrowth in renal transplant recipients receiving Cyclosporin A

AIM: Levels of interleukin-1alpha (IL-1alpha) are elevated in periodontal inflammation. IL-1A gene polymorphisms are associated with inflammatory diseases. This study aimed to investigate IL-1A gene polymorphism in Cyclosporin A (CsA)-treated renal transplant patients and investigate the association between this polymorphism and gingival crevicular fluid (GCF) levels of several cytokines. MATERIALS AND METHODS: Fifty-one renal transplant patients on CsA treatment (25 with and 26 without gingival overgrowth) and 29 healthy controls were recruited for the study. Demographic, pharmacological and periodontal parameters were recorded and gingival overgrowth was assessed. RESULTS: Multiple regression analysis showed that genotype was significantly associated with gingival overgrowth (p=0.02). Carriage of the IL-1A (-889) T allele was strongly protective [95% confidence interval (CI): 0.046-0.77], although not significantly associated with IL-1alpha protein levels in GCF. IL-1alpha, IL-1beta and IL-8, but not IL-6, were detected in GCF of CsA-treated patients, but none of them was significantly associated with gingival overgrowth. CONCLUSIONS: This study is the first to associate a gene polymorphism as a risk factor for CsA-induced gingival overgrowth in renal transplant patients, demonstrating that IL-1A polymorphism might alter individual susceptibility to CsA. However, there was no association between GCF cytokine levels and the presence of gingival overgrowth or patient IL-1A genotype.     

Levels of leukotriene B4 and platelet activating factor in gingival crevicular fluid in renal transplant patients receiving cyclosporine A

BACKGROUND: Cyclosporine A (CsA) is a potent immunosuppressant effectively used to prevent organ transplant rejection and also to treat several systemic 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 the present study was to identify the role of leukotriene B4 (LTB4) and platelet activating factor (PAF) in the pathogenesis of CsA GO. METHODS: LTB4 and PAF levels were detected in gingival crevicular fluid (GCF) samples from renal transplant patients receiving CsA therapy and exhibiting CsA GO, from patients with gingivitis and from periodontally healthy subjects. Plaque index, papilla bleeding index, and hyperplastic index were recorded at each study site. GCF samples and clinical data were obtained from: 2 sites exhibiting CsA GO (CsA GO+) and 2 sites not exhibiting CsA GO (CsA GO-) in each CsA-treated patient; 2 diseased sites in each patient with gingivitis; and 2 healthy sites in each subject with clinically healthy periodontium. LTB4 was extracted from the samples by solid-phase method using C18 cartridge and purified by high-performance liquid chromatographic (HPLC) method and analyzed by radioimmunoassay (RIA). PAF was extracted from GCF samples passing through amberlit resin columns, purified by HPLC, and analyzed by RIA. RESULTS: Total amounts of LTB4 and PAF in GCF were higher in CsA GO+ sites compared to the healthy sites from healthy controls. However, the amount of LTB4 and PAF elevation in CsA GO+ sites was not significantly higher than those in diseased sites. Clinical degrees of gingival inflammation were also similar between CsA GO+ and diseased sites. LTB4 and PAF total amounts in GCF were higher in CsA GO+ sites compared to CsA GO- sites in the same subjects, but this difference just failed to reach significance. Similar findings were obtained with concentration data. CONCLUSIONS: The results of this study indicate that CsA therapy does not have a significant effect on GCF LTB4 and PAF levels and that gingival inflammation seems to be the main reason for their elevation. In CsA-treated patients, alterations in LTB4 and PAF levels might play a role in CsA GO through some asyet unknown mechanism. To our knowledge, this is the first report describing the levels of lipid mediators in GCF of CsA-treated patients. We assume that further studies will contribute to the understanding of the pathogenesis of CsA-induced gingival overgrowth.     

Immunohistochemical analysis of epidermal growth factor receptor in cyclosporin A-induced gingival overgrowth

Cyclosporin A (CsA)-induced gingival overgrowth represents a tissue of fibrosis and epidermal growth factor (EGF) has been shown to induce extracellular matrix synthesis by fibroblasts. The purpose of this study was to evaluate the expression of EGF-receptor (EGF-r) in frozen sections of CsA-induced overgrown gingival tissue using immunohistochemical and semiquantitative techniques. Gingival biopsies were obtained from 12 renal transplant patients receiving CsA as well as 9 systemically and periodontally healthy individuals. Immunohistochemical staining procedures were carried out in frozen sections of gingival tissue and the expression of EGF-r was compared between the two study groups. The expression of EGF-r was more pronounced in the oral gingival epithelium of CsA-induced overgrown gingiva as compared to those of the clinically healthy gingival specimens. The reactivity in the inflammatory infiltrate and connective tissue cells of both of the study groups was similar. In conclusion, the results of the present study may suggest that CsA affects EGF-r metabolism in gingival keratinocytes resulting in an increased number of cell surface receptors, which may eventually play a role in the pathogenesis of gingival tissue alterations.     

Immunohistochemical analysis of epidermal growth factor receptor in cyclosporin A-induced gingival overgrowth

Cyclosporin A (CsA)induced gingival overgrowth represents a tissue of fibrosis and epidermal growth factor (EGF) has been shown to induce extracellular matrix synthesis by fibroblasts. The purpose of this study was to evaluate the expression of EGF-receptor (EGF-r) in frozen sections of CsA-induced overgrown gingival tissue using immunohistochemical and semiquantitative techniques. Gingival biopsies were obtained from 12 renal transplant patients receiving CsA as well as 9 systemically and periodontally healthy individuals. Immunohistochemical staining procedures were carried out in frozen sections of gingival tissue and the expression of EGF-r was compared between the two study groups. The expression of EGF-r was more pronounced in the oral gingival epithelium of CsA-induced overgrown gingiva as compared to those of the clinically healthy gingival specimens. The reactivity in the inflammatory infiltrate and connective tissue cells of both of the study groups was similar. In conclusion, the results of the present study may suggest that CsA affects EGF-r metabolism in gingival keratinocytes resulting in an increased number of cell surface receptors, which may eventually play a role in the pathogenesis of gingival tissue alterations.     

Immunohistochemical analysis of lymphocyte subpopulations in cyclosporin A-induced gingival overgrowth

BACKGROUND: Cyclosporin A (CsA) is an immunosuppressive agent that is known to induce gingival overgrowth (GO). Pharmacological, genetic, immunologic, and inflammatory factors seem to be involved in the complex pathogenesis of drug-induced GO. Lymphocyte subpopulations in human gingival connective tissue have been implicated in the pathogenesis of inflammatory periodontal diseases. One purpose of this study was to quantify CD4, CD8-, CD57-, and epithelial membrane antigen (EMA)-positive cells in the gingiva of renal transplant recipients treated with CsA, and compare them to findings in healthy controls. A second aim was to correlate cell numbers with clinical findings. METHODS: The study included 19 kidney recipients who were taking CsA and had significant GO (CsAGO+), 13 recipients who were taking CsA but showed no GO (CsAGO-), and 14 systemically healthy individuals with gingivitis (C). Sections from gingival biopsies were incubated with monoclonal antibodies for CD4, CD8, EMA, and CD57, and then analyzed using the avidin-biotin complex method. In each specimen, the mononuclear cell types were quantified and their distribution was evaluated in 3 separate tissue zones: S = subepithelial connective tissue beneath the sulcular epithelium; O = subepithelial connective tissue beneath the oral epithelium; and M = middle connective tissue. RESULTS: There were no significant differences among the groups with respect to the numbers of CD4+ and CD8+ cells in each of the 3 zones (P >0.05). In zone S, the CsAGO+ group had significantly more EMA-positive cells than either the C or CsAGO- groups (P <0.05). There were significant differences among the groups regarding numbers of CD57+ (natural killer) cells in zone M, with the lowest cell numbers in the CsAGO+ patients (P<0.05). CONCLUSIONS: The results showed that low numbers of natural killer cells are important in the expression of plaque-induced inflammatory changes in CsA-associated GO. It appears that these cells may influence the drug's ability to induce proliferative activity.     

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.     

Hereditary gingival fibromatosis and expression of Ki-67 antigen: a case report

BACKGROUND: Hereditary gingival fibromatosis (HGF) is a fibrotic enlargement of the gingiva. The mechanism that leads to the accumulation of abnormal amounts of gingival tissue in HGF is still unknown. The aim of this report was to present the clinical and histopathologic characteristics of a patient with gingival fibromatosis and to evaluate the proliferation of HGF fibroblasts. METHODS: We examined the proliferation rate of fibroblasts in this case by using Ki-67 immunohistochemical staining and compared the rate to fibroblasts of non-fibromatosis gingival tissues from 5 healthy patients serving as controls. RESULTS: There were no Ki-67-positive cells in the lesional tissue, and the control gingiva revealed no immunostaining. The number of Ki-67 antigen-positive epithelial cell nuclei was observed to be low in the basal cell layers of hyperplastic gingival epithelia, similar to the control group. CONCLUSIONS: In the present case, there was no increase in the proliferation rate of lesional fibroblasts observed by Ki-67 immunohistochemical staining as a proliferation marker; only the epithelium was stained. It seems likely that the underlying mechanism of HGF may be an increase in the biosynthesis of collagen and glycosaminoglycans rather than cell proliferation.