Ye Ping, Nadkarni Mangala A, Simonian Mary, Hunter Neil
Institute of Dental Research, Westmead Millennium Institute and Westmead Centre for Oral Health, Westmead Hospital, Westmead, NSW 2145, Australia.
BMC Cell Biol. 2009 Jan 13;10:2. doi: 10.1186/1471-2121-10-2.
Control of intercellular penetration of microbial products is critical for the barrier function of oral epithelia. We demonstrated that CD24 is selectively and strongly expressed in the cells of the epithelial attachment to the tooth and the epithelial lining of the diseased periodontal pocket and studies in vitro showed that CD24 regulated expression of the epithelial intercellular adhesion protein E-cadherin.
In the present study, the barrier function of oral epithelial cell monolayers to low molecular weight dextran was assayed as a model for the normal physiological function of the epithelial attachment to limit ingress of microbial products from oral microbial biofilms. Paracellular transfer of low molecular weight dextran across monolayers of oral epithelial cells was specifically decreased following incubation with anti-CD24 peptide antibody whereas passage of dextran across the monolayer was increased following silencing of mRNA for CD24. Changes in barrier function were related to the selective regulation of the genes encoding zonula occludens-1, zonula occludens-2 and occludin, proteins implicated in tight junctions. More particularly, enhanced barrier function was related to relocation of these proteins to the cell periphery, compatible with tight junctions.
CD24 has the constitutive function of maintaining expression of selected genes encoding tight junction components associated with a marginal barrier function of epithelial monolayers. Activation by binding of an external ligand to CD24 enhances this expression but is also effective in re-deployment of tight junction proteins that is aligned with enhanced intercellular barrier function. These results establish the potential of CD24 to act as a potent regulator of the intercellular barrier function of epithelia in response to local microbial ecology.
控制微生物产物的细胞间渗透对于口腔上皮的屏障功能至关重要。我们证明了CD24在与牙齿的上皮附着细胞以及患病牙周袋的上皮衬里中选择性且强烈地表达,并且体外研究表明CD24调节上皮细胞间粘附蛋白E-钙粘蛋白的表达。
在本研究中,检测了口腔上皮细胞单层对低分子量葡聚糖的屏障功能,以此作为上皮附着正常生理功能的模型,以限制口腔微生物生物膜中微生物产物的进入。用抗CD24肽抗体孵育后,低分子量葡聚糖跨口腔上皮细胞单层的细胞旁转运特异性降低,而在CD24的mRNA沉默后,葡聚糖跨单层的通过率增加。屏障功能的变化与编码闭合蛋白1、闭合蛋白2和闭合蛋白的基因的选择性调节有关,这些蛋白与紧密连接有关。更具体地说,增强的屏障功能与这些蛋白重新定位到细胞周边有关,这与紧密连接相符。
CD24具有维持与上皮单层边缘屏障功能相关的紧密连接成分的选定编码基因表达的组成性功能。外部配体与CD24结合激活可增强这种表达,但在重新部署与增强的细胞间屏障功能一致的紧密连接蛋白方面也有效。这些结果确定了CD24作为上皮细胞间屏障功能的有效调节剂以响应局部微生物生态的潜力。