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

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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.