Butyric acid, an extracellular metabolite from periodontopathic bacteria, induces apoptosis in murine and human T- and B-cells, whereas intact gingival fibroblasts isolated from healthy humans are resistant to butyric-acid-induced apoptosis. We examined the susceptibility of inflamed gingival fibroblasts isolated from adult persons with periodontitis to butyric-acid-induced apoptosis. Butyric acid significantly suppressed the viability of inflamed gingival fibroblasts and induced apoptosis in a dose-dependent manner. The incubation of inflamed gingival fibroblasts with butyric acid induced DNA fragmentation and apoptotic changes such as chromatin condensation, hypodiploid nuclei, and mitochondrial injury. Furthermore, butyric-acid-induced apoptosis in inflamed gingival fibroblasts was reduced by caspase-3/7, -6, -8, and -9 inhibitors. Thus, inflamed gingival fibroblasts from adult persons with periodontitis appear to be highly susceptible to mitochondria- and caspase-dependent apoptosis induced by butyric acid, compared with healthy gingival fibroblasts.
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References
1.
Botta GA, Radin L, Costa A, Schito G, Blasi G -1985-. Gas-liquid chromatography of the gingival fluid as an aid in periodontal diagnosis. J Periodontal Res20:450–457.
2.
Chen Y, Zychlinsky A -1994-. Apoptosis induced by bacterial pathogens. Microb Pathog17:203–212.
3.
Cheng Y, Chaturvedi R, Asim M, Bussiere FI, Xu H, Casero RA Jr, et al. -2005-. Helicobacter pylori-induced macrophage apoptosis requires activation of ornithine decarboxylase by c-Myc. J Biol Chem280:22492–22496; published erratum in J Biol Chem 280:28827, 2005.
4.
Cryns VL, Bergeron L, Zhu H, Li H, Yuan J -1996-. Specific cleavage of alpha-fodrin during Fas- and tumor necrosis factor-induced apoptosis is mediated by an interleukin-1-beta converting enzyme/Ced-3 protease distinct from poly-ADP-ribose- polymerase protease. J Biol Chem271:31277–31282.
5.
Ekuni D, Tomofuji T, Yamanaka R, Tachibana K, Yamamoto T, Watanabe T -2005-. Initial apical migration of junctional epithelium in rats following application of lipopolysaccharide and proteases. J Periodontol76:43–48.
6.
Gamonal J, Bascones A, Acevedo A, Blanco E, Silva A -2001-. Apoptosis in chronic adult periodontitis analyzed by in situ DNA breaks, electron microscopy, and immunohistochemistry. J Periodontol72:517–525.
7.
Jewett A, Hume WR, Le H, Huynh TN, Han YW, Cheng G, et al. -2000-. Induction of apoptotic cell death in peripheral blood mononuclear and polymorphonuclear cells by an oral bacterium, Fusobacterium nucleatum.Infect Immun68:1893–1898.
8.
Koulouri O, Lappin DF, Radvar M, Kinane DF -1990-. Cell division, synthetic capacity and apoptosis in periodontal lesions analysed by in situ hybridization and immunohistochemistry. J Clin Periodontol26:552–559.
9.
Kronenberger B, Wagner M, Herrmann E, Mihm U, Piiper A, Sarrazin C, et al. -2005-. Apoptotic cytokeratin 18 neoepitopes in serum of patients with chronic hepatitis C. J Viral Hepat12:307–314.
10.
Kurita-Ochiai T, Fukushima K, Ochiai K -1995-. Volatile fatty acids, metabolic by-products of periodontopathic bacteria, inhibit lymphocyte proliferation and cytokine production. J Dent Res74:1367–1373.
11.
Kurita-Ochiai T, Fukushima K, Ochiai K -1997-. Butyric acid-induced apoptosis of murine thymocytes, splenic T cells, and human Jurkat T cells. Infect Immun65:35–41.
12.
Kurita-Ochiai T, Fukushima K, Ochiai K -1998-. Volatile fatty acid, a metabolic by-product of periodontopathic bacteria, induces apoptosis in WEHI 231 and RAJI B lymphoma cells and splenic B cells. Infect Immun66:2587–2594.
13.
Kurita-Ochiai T, Ochiai K, Fukushima K -2001-. Butyric acid-induced T-cell apoptosis is mediated by caspase-8 and -9 activation in a Fas-independent manner. Clin Diagn Lab Immunol8:325–332.
14.
Kurita-Ochiai T, Ochiai K, Suzuki N, Otsuka K, Fukushima K -2002-. Human gingival fibroblasts rescue butyric acid-induced T-cell apoptosis. Infect Immun70:2361–2367.
15.
Lazebnik YA, Kaufmann SH, Desnoyers S, Poirier GG, Earnshaw WC -1994-. Cleavage of poly-ADP-ribose- polymerase by a proteinase with properties like ICE. Nature371:346–347.
16.
Lazebnik YA, Takahashi A, Moir RD, Goldman RD, Poirier GC, Kaufmann SH, et al. -1995-. Studies of the lamin proteinase reveal multiple parallel biochemical pathways during apoptotic execution. Proc Natl Acad Sci USA92:9042–9046.
17.
Margolis HC, Duckworth JH, Moreno EC -1988-. Composition and buffer capacity of pooled starved plaque fluid from caries-free and caries-susceptible individuals. J Dent Res67:1476–1482.
18.
Meyaard L, Otto SA, Jonker RR, Mijnster MJ, Keet RP, Miedema F -1992-. Programmed death of T cells in HIV-1 infection. Science257:217–219.
19.
Naleway C, Chou H, Manus T, Goodman C, Robinson P, Singer R -1989-. Assessment of the potential relationship between levels of SCFA found in subgingival plaque and periodontal health -abstract-. J Dent Res68-Spec Iss-:121.
20.
Ochiai K, Kurita-Ochiai T -2003-. Volatile fatty acids-induced apoptosis modulates immunoresponses in gingival tissue. Dent Jpn39:29–33.
21.
Sakahira H, Enari M, Nagata S -1998-. Cleavage of CAD inhibitor in CAD activation and DNA degradation during apoptosis. Nature391:96–99.
22.
Sawa T, Nishimura F, Ohyama H, Takahashi K, Takashiba S, Murayama Y -1999-. In vitro induction of activation-induced cell death in lymphocytes from chronic periodontal lesions by exogenous Fas ligand. Infect Immun67:1450–1454.
23.
Terai C, Kornbluth RS, Pauza CD, Richman DD, Carson DA -1991-. Apoptosis as a mechanism of cell death in cultured T lymphoblasts acutely infected with HIV-1. J Clin Invest87:1710–1715.
24.
Zychlinsky A, Prevost MC, Sansonetti PJ -1992-. Shigella flexneri induces apoptosis in infected macrophages. Nature358:167–169.
