Human gingival fibroblasts rescue butyric acid-induced T-cell apoptosis.
We previously demonstrated that butyric acid, an extracellular metabolite from periodontopathic bacteria, induces cytotoxicity and apoptosis in murine thymocytes, splenic T cells, and human Jurkat T cells. In this study, we used a cell-to-cell interaction system to examine the contribution of gingival fibroblasts to the regulation of T-cell death induced by butyric acid. Butyric acid slightly suppressed fibroblast viability in a concentration-dependent fashion. However, DNA fragmentation assays indicated that butyric acid did not induce apoptosis for up to 21 h in human gingival fibroblasts (Gin 1, F41-G, and H. pulp cells). The culture supernatants were assayed for interleukin 1alpha (IL-1alpha), IL-1beta, IL-6, IL-8, IL-11, tumor necrosis factor alpha, and transforming growth factor beta, but only the IL-6, IL-8, and IL-11 levels were significantly increased by addition of butyric acid. Butyric acid- or Fas-induced Jurkat-cell apoptosis was attenuated when Jurkat cells were cocultured with either F41-G or Gin 1 cells that had been preincubated for 6 h with butyric acid. IL-8 slightly stimulated butyric acid- or Fas-induced Jurkat-cell apoptosis in a dose-dependent manner, although a low dose of IL-8 had a mildly inhibitory effect on apoptosis. In contrast, IL-6 and IL-11 significantly suppressed butyric acid- or Fas-induced apoptosis in a dose-dependent fashion. Furthermore, the addition of monoclonal antibodies against human IL-6 and IL-11 to cocultures of gingival fibroblasts and Jurkat cells partially eliminated T-cell recovery. These results suggest that the proinflammatory cytokines such as IL-6 and IL-11, produced in fibroblasts stimulated with butyric acid, are involved in the attenuation of T-cell apoptosis by gingival fibroblasts.
Kurita-Ochiai
Tomoko
T
Department of Microbiology, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba 271-8587, Japan. tkurita@mascat.nihon-u.ac.jp
Ochiai
Kuniyasu
K
Suzuki
Naoto
N
Otsuka
Kichibee
K
Fukushima
Kazuo
K
D017209:Apoptosis / Q000187:drug effects*; D020148:Butyric Acid / Q000633:toxicity*; D002450:Cell Communication; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D005347:Fibroblasts / Q000502:physiology*; D005881:Gingiva / Q000166:cytology*; D006801:Humans; D017370:Interleukin-11 / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology; D016209:Interleukin-8 / Q000502:physiology; D010510:Periodontal Diseases / Q000209:etiology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology
D016207:Cytokines; D017370:Interleukin-11; D015850:Interleukin-6; D016209:Interleukin-8; D020148:Butyric Acid