歯周病変局所における上皮細胞間接着機構に関与する分子群の発現解析
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Tight junctions form the apical junctional complex in the epithelium and are essential for the tight sealing of cellular sheets. They are composed of three major integral membrane proteins, i.e., occludin, claudins, and junctional adhesion molecules. Expression patterns of claudins are tissue specific and most tissues express multiple claudins. The combination of claudin proteins is thought to determine the strength of the tight junctions of the tissue ; however, the expression pattern of the claudin family in human gingival epithelium remains unclear. The aim of this study was to examine the expression pattern of the claudin family, E-cadherin, JAM-A and occludin, in chhronic inflammatory lesions of gingival epithelium. Expression levels of mRNA in human gingival tissue from healthy gingivae and inflammation gingivae (probing depth>6mm, sulcular bleeding on probing) were analyzed by RT-PCR. To determine the expression patterns of tight junction molecules in situ, claudin-10, E-cadherin and JAM-A was detected by immunohistochemistry and in situ hybridization. Sa3 (squamous carcinoma cell derived from human oral cancer) was cultured in the monolayer in the presence or absence of TNF-α and IL-13, and the expression of the claudin family and other TJ-related protein were detected by RT-PCR and flow cytometry. To confirm whether inflammatory cytokines, TNF-α and IL-13, affect the functional integrity of Sa3 cell layers, transepithelial electrical resistance (TER) and transepithelial cell permeability were measured. RT-PCR analysis showed that claudin-1, -4, -7 and-12 were expressed but claudin-2, -6, -9 and -11 were not expressed in human normal gingival tissues. Of particular significance, the expression level of claudin-10 was increased in inflamed gingival tissues compared with normal gingival tissues. In situ hybridization and immunohistochemical analysis showed that claudin-10 expression was strongly detected in the basal layer of the epithelium in inflamed gingival tissues. In a monolayer culture of Sa3, TNF-α and IL-13 decreased the mRNA expression levels of E-cadherin, occludin and JAM-A in a dose-dependent manner, and increased those of claudin-2, 3, 4 and 8. In addition, TNF-α and IL-13 decreased TER and increased the transepithelial cell permeability of monolayer Sa3 cells. These data suggest that periodontal inflammatory response induces claudin-10 expression and leads to modification of the function of gingival epithelium. This alteration in inflamed gingival tissues may contribute to the pathogenesis of periodontitis.