Apoptosis induced by Short-chain Fatty Acids Modulates Immunoresponses: Role of Cell-to-cell Communication in Inhibiting Butyric Acid-induced T Cell Apoptosis

  • Ochiai Kuniyasu
    Department of Bacteriology, Nihon University, School of Dentistry
  • Kurita-Ochiai Tomoko
    Department of Microbiology and Immunology, Nihon University, School of Dentistry at Matsudo

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Butyric acid present in the culture filtrates of Porphyromonas gingivalis, Prevotella loescheii and Fusobacterium nucleatum induced cytotoxicity and apoptosis in murine thymocytes, splenic T cells, and human Jurkat T cells. A pronounced accumulation of ROS occurred during butyric acid-induced apoptosis. Butyric acid induced apoptosis via the mitochondrial apoptotic pathway, e.g. cytochrome c, AIF, and Smac, and by the ceramide pathway. Up-regulation of JNK and p38, and down-regulation of ERK occurred immediately after butyric acid treatment. In microarray analysis, butyric acid treatment resulted in increased expression of the proapoptotic gene, whereas the expression of anti-apoptotic mediators was decreased. These data suggest that butyric acid is an apoptosis-inducing agent in most lymphoreticular cells. In contrast, epithelial cells and fibroblasts were insensitive to butyric acid. Fibroblasts from healthy gingival tissue rescued butyric acid-induced T cell apoptosis via proinflammatory cytokines such as IL-6 and IL-11, which were produced by the fibroblasts stimulated by butyric acid. Furthermore, the T cell apoptosis was also down-regulated by T cell adhesion to gingival fibroblasts through interaction with CD44, VLA-2, and VLA-5 expressed on T cells stimulated with butyric acid. Also, gingival fibroblasts from periodontal patients were highly susceptible to apoptosis induced by butyric acid when compared to healthy gingival fibroblasts. In conclusion, since short-chain fatty acids produced by periodontopathic bacteria induce apoptosis in immunological cells and the fibroblasts from periodontal patients, the results strongly suggested that they are concerned with the progress of periodontal disease.<br>

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