Apoptosis induced by butyric acid modulates immunoresponses : Role of epitherial cells and fibroblasts in inhibiting butyric acid-induced T cell apoptosis

近年来，有报道称牙周病菌引起局部慢性疾病，不仅可能是病灶感染的来源，而且可能是炎症物质的来源。人们认识到牙周病是传染性的，牙周组织的破坏是由特定的厌氧细菌和宿主免疫机制相互作用造成的。短链脂肪酸（SCFA）是牙周病菌产生的一种易渗透到口腔黏膜的物质，对T细胞和b细胞的增殖及细胞因子的产生有很大的抑制作用。丁酸是由牙龈卟啉单胞菌、中间普雷沃氏菌和核梭杆菌产生的，具有免疫调节特性。丁酸诱导小鼠和人T细胞凋亡。我们报道了丁酸诱导的T细胞凋亡是由神经酰胺的产生、线粒体中的ROS合成和丝裂原激活的蛋白激酶级联中的JNK激活介导的。我们证明了人牙龈成纤维细胞（HGF）通过在丁酸刺激下成纤维细胞产生的促炎细胞因子，如IL-6和IL-11，来挽救丁酸诱导的t细胞凋亡。我们评估了T细胞与HGF的粘附是否调节了T细胞对丁酸诱导的凋亡的敏感性。添加丁酸后，HGF黏附Jurkat细胞的数量明显增加。粘附在Gin-1细胞上的Jurkat细胞均为活细胞，未粘附的Jurkat细胞呈凋亡状态。丁酸刺激的T细胞上表达的黏附分子CD44、VLA-2和VLA-5与HGF的黏附作用相互作用，从而下调丁酸诱导的T细胞凋亡。丁酸是引起牙龈炎症的病原体，可能通过牙龈组织中T细胞和b细胞的凋亡发挥免疫调节作用。然而，HGF可以挽救丁酸诱导的粘膜厌氧细菌感染炎症部位的t细胞凋亡。

Recently, it was reported that periodontpathic bacteria cause local chronic disease, could be not only a source of focus infection, but also holding resources of inflamed materials. It is recognized that periodontal diseases are infectious and that periodontal tissue breakdown results from the interaction of specific anaerobic bacteria and host immune mechanisms. Short-chain fatty acids (SCFA) produced by periodontpathic bacteria, easily penetrate into oral mucosa and greatly inhibit T- and B-cell proliferation and cytokine production. Butyric acid is produced by Porphyrpmonas gingivalis, Prevotella intermedia and Fusobacterium nucleatum, and exerts immunomodulatory properties. Butyric acid induces apoptosis in murine and human T cells. We reported that Butyric acid-induced T cell apoptosis is mediated by ceramide production, ROS synthesis in mitochondria, and JNK activation in the mitogen-activated protein kinase cascade. We demonstrated that human gingival fibroblasts (HGF) rescue butyric acid-induced T-cell apoptosis via the proinflammatory cytokines, such as IL-6 and IL-11, which were produced in fibroblasts stimulated with butyric acid. We assessed whether the T cell adhesion to HGF regulates the susceptibility of T cells to butyric acid-induced apoptosis. The number of Jurkat cells adhered to HGF was significantly increased by addition of butyric acid. All Jurkat cells adhered to Gin-1 cells were live cells in contrast to non-adhered cells drop into apoptosis. Butyric acid-induced T-cell apoptosis is down-regulated by the adhesion to HGF through the interaction with the adhesion molecule such as CD44, VLA-2 and VLA-5, expressed on T cells stimulated with butyric acid. Butyric acid is a causative agent in gingival inflammation and may exert immunomodulation through T- and B-cell apoptosis in gingival tissue. However, HGF rescue butyric acid-induced T-cell apoptosis at the inflammatory sites of anaerobic-bacterial infection in mucous membrane.