The induction expression of human β-defensins in gingival epithelial cells and fibroblasts

ObjectiveThe gingival epithelial cells and fibroblasts can produce antimicrobial peptides when stimulated by inflammatory cytokines. The purpose of the present study was to test whether gingival keratinocytes and gingival fibroblasts respond differently to inflammatory cytokine activation. This will enable us to understand the chronic inflammatory response in the process of periodontal disease.DesignGingival keratinocytes and fibroblasts were isolated and treated with different concentrations of IL-1β and quantitative real-time PCR was performed to evaluate the induced expressions of hBD-1, hBD-2 and hBD-3. The induced response was compared between the gingival epithelial cells and fibroblasts. The inhibitors of p38 protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) were applied to explore the molecular mechanism during the induction of hBDs in both cells.ResultsThe results showed that the hBDs expressions were found to be induced by different concentrations of IL-1β, but with several differences between gingival epithelial cells and fibroblasts. The hBDs mRNA expression in gingival fibroblasts was more sensitive compared with keratinocytes to different concentrations of IL-1β. The hBD-1 and hBD-3 expressions in these two cells were down-regulated by IL-1β and hBD-2 expression was up-regulated. The inflammatory cytokine IL-1β had dual effect on hBDs expression.ConclusionsThe gingival epithelial cells and fibroblasts respond differently to the inflammatory cytokine IL-1β which indicated different roles played by the two cells in the host defense. The dual effect of IL-1β on hBDs expression may contribute to the defensins down-regulation in periodontal disease.     

MiR-200b suppresses TNF-α-induced AMTN production in human gingival epithelial cells

Odontology - Amelotin (AMTN) is an enamel protein that is localized in junctional epithelium (JE) of gingiva and suggested to be involved in the attachment between JE and tooth enamel. MicroRNA is...     

Estrogen regulates DNA synthesis in human gingival epithelial cells displaying strong estrogen receptor β immunoreactivity

Nebel D, Bratthall G, Ekblad E, Norderyd O, Nilsson B‐O. Estrogen regulates DNA synthesis in human gingival epithelial cells displaying strong estrogen receptor β immunoreactivity. J Periodont Res 2011; 46: 622–628. © 2011 John Wiley & Sons A/S Background and Objective: Estrogen acts via estrogen receptor (ER) α and β. The expression pattern of ERs and their importance in gingival tissues are not fully understood. In this study, we investigate gingival ER expression and effects of estrogen on gingival epithelial cell proliferation. Material and Methods: Gingival biopsies were obtained from both healthy and diseased sites in three male and three female subjects. Expression of ERα and β was determined by immunohistochemistry. Effects of 17β‐estradiol (E₂) on cell proliferation, monitored by measuring DNA synthesis, were studied in cultured human gingival epithelial HGEPp.05 cells. Results: Estrogen receptor β, but not ERα, immunoreactivity was demonstrated in nuclei of epithelial cells in all layers of the gingival epithelium, but also in cells of the lamina propria. No differences were observed between male and female subjects. The same pattern, i.e. high ERβ expression but no ERα expression, was observed in both healthy and diseased sites within each individual. No differences in the intensity of the ERβ immunoreactive signal and the number of ERβ‐positive nuclei were observed between healthy and diseased gingiva. Treatment with a physiological concentration of E₂ (10 nm ) had no effect on DNA synthesis in ERβ‐ and ERα‐expressing HGEPp.05 cells. In contrast, E₂ at high concentrations (500 nm and 10 μm ) reduced DNA synthesis by 60–70%. Conclusion: Human gingival epithelial cells display strong ERβ but low ERα immunoreactivity both in vivo and in culture. Estrogen attenuates gingival epithelial cell DNA synthesis at high but not low concentrations, suggesting a concentration‐dependent mechanism.     

Does expression of inducible nitric oxide synthase correlate with severity of oral epithelial dysplasia?

The small molecule nitric oxide (NO) has generated an exponential amount of research since its discovery as a biological messenger in 1987. It has a vast number of actions, many of which are poorly understood. It has been studied in a variety of human cancers and has been implicated both in tumour promotion and inhibition. Although NO is produced by three distinct isoforms of the enzyme nitric oxide synthase (NOS), most cancer research is directed towards the calcium-independent form, iNOS which following induction, produces much higher quantities of NO than the other two. In this study the expression of iNOS is assessed by immunohistochemistry in 26 cases of oral epithelial dysplasia ranging in severity from mild to severe. iNOS staining was found in all 26 cases of dysplasia with the degree of staining correlating to the severity of dysplasia (p < 0.001). There was no iNOS staining seen in adjacent normal epithelium. The possible role of iNOS in the complex transformation from dysplasia to invasive oral cancer and the clinical applications are discussed.     

Mapping dynamic epithelial cell proliferative activity within the oral cavity of man: a new insight into carcinogenesis?

Our aim was to characterize epithelial cell proliferative activity within the oral cavity and to find out if there were differences between sites with high and low incidence of cancer. A total of 105 samples of clinically normal mucosa were harvested from various intra-oral sites. Excised specimens were incubated in vitro with tritiated thymidine and bromodeoxyuridine to 'double label' cells undergoing DNA synthesis, and enable calculation of the duration of S phase and estimation of variables of cell flux to and from S. Mean labelling indices (percentage of cells within the S phase of the cell cycle) were highest in the floor of mouth (12.3%) and ventral tongue (10.1%), while activity was lowest in the dorsum of tongue (4.3%) and the palate (7.2%), P<0.001. In general, both cell influx and the duration of S increased proportionally to the labelling index. Sites with a high incidence of cancer were characterized by high labelling indices, increased cell influx and a prolonged S phase.     

Increased nuclear ?-catenin expression in oral potentially malignant lesions: A marker of epithelial dysplasia

Background

Deregulation of ?-catenin is associated with malignant transformation; however, its relationship with potentially malignant and malignant oral processes is not fully understood. The aim of this study was to determine and compare the nuclear ?-catenin expression in oral dysplasia and oral squamous cell carcinoma (OSCC).

Material and Methods

Cross sectional study. Immunodetection of ?-catenin was performed on 72 samples, with the following distribution: 21 mild dysplasia, 12 moderate dysplasia, severe dysplasia 3, 36 OSCC including 19 well differentiated, 15 moderately differentiated and 2 poorly differentiated. Through microscopic observation the number of positive cells per 1000 epithelial cells was counted. For the statistical analysis, the Kruskal Wallis test was used.

Results

Nuclear expression of ?-catenin was observed in all samples with severe and moderate dysplasia, with a median of 267.5, in comparison to mild dysplasia whose median was 103.75. Only 10 samples (27.7%) with OSCC showed nuclear expression, with statistically significant differences between groups (p < 0.05).

Conclusions

Our results are consistent with most of the reports which show increased presence of ?-catenin in severe and moderate dysplasia compared to mild dysplasia; however the expression of nuclear ?-catenin decreased after starting the invasive neoplastic process. This suggests a role for this protein in the progression of dysplasia and early malignant transformation to OSCC. Immunodetection of ?-catenin could be a possible immune marker in the detection of oral dysplasia. Key words:Oral squamous cell carcinoma (OSCC), ?-catenin, oral dysplasia.