1887

Abstract

It has previously been reported that the murine macrophage cell line J774.1 and the human oral epithelial cell line KB undergo apoptosis as a result of infection. Recent studies have demonstrated that apoptosis regulation is modulated by multiple phosphorylation of several different protein kinases, including the major subtypes of the mitogen-activated protein kinase (MAPK) family. The MAPK family promotes cell survival and/or proliferation in response to growth factor stimulation, or apoptosis in response to various stress stimuli. The primary objective of the present investigation was to clarify whether human immune cells undergo apoptosis following infection and, if so, to establish the involvement of the MAPK family. Human monocytic THP-1 cells were infected with in microtubes. Lactate dehydrogenase release into the culture supernatant and DNA fragmentation in the cells were monitored. DNA fragmentation was also identified by agarose gel electrophoresis. Cell death following infection occurred by apoptosis, shown by an increase in the proportion of fragmented DNA and the typical ladder pattern of DNA fragmentation indicative of apoptosis. Furthermore, p38 MAPK activity and tumour necrosis factor alpha (TNF-α) levels increased following infection. In contrast, cell death and TNF-α levels in infected cells decreased upon addition of a p38 inhibitor or an anti-TNF-α antibody. However, exogenous TNF-α could not induce apoptosis in uninfected THP-1 cells. Interestingly, p38 MAPK activity diminished in the presence of anti-TNF-α antibody. These findings indicated that infection induces apoptosis in THP-1 cells and that p38 MAPK activity is directly involved in apoptosis. TNF-α may play an indirect role in apoptosis via enhanced p38 MAPK activity. -induced apoptosis of human immune cells may be important in terms of initiation and progression of periodontal diseases.

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2005-03-01
2024-03-28
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References

  1. Buscher M., Rahmsdorf H. J., Litfin M., Karin M., Herrlich P. 1988; Activation of the c-fos gene by UV and phorbol ester: different signal transduction pathways converge to the same enhancer element. Oncogene 3:301–311
    [Google Scholar]
  2. Cohen J. J., Duke R. C., Fadok V. A., Sellins K. S. 1992; Apoptosis and programmed cell death in immunity. Annu Rev Immunol 10:267–293 [CrossRef]
    [Google Scholar]
  3. Dean J. L., Brook M., Clark A. R., Saklatvala J. 1999; p38 mitogen-activated protein kinase regulates cyclooxygenase-2 mRNA stability and transcription in lipopolysaccharide-treated human monocytes. J Biol Chem 274:264–269 [CrossRef]
    [Google Scholar]
  4. Fukunaga M., Tsuruda K. 2001; Actinobacillus actinomycetemcomitans induces lethal effects on the macrophage-like human cell line U937. Oral Microbiol Immunol 16:284–289 [CrossRef]
    [Google Scholar]
  5. Hobbie S., Chen L. M., Davis R. J., Galan J. E. 1997; Involvement of mitogen-activated protein kinase pathways in the nuclear responses and cytokine production induced by Salmonella typhimurium in cultured intestinal epithelial cells. J Immunol 159:5550–5559
    [Google Scholar]
  6. Ip Y. T., Davis R. J. 1998; Signal transduction by the c-Jun N-terminal kinase (JNK) – from inflammation to development. Curr Opin Cell Biol 10:205–219 [CrossRef]
    [Google Scholar]
  7. Kato S., Muro M., Akifusa S., Hanada N., Semba I., Fujii T., Kowashi Y., Nishihara T. 1995; Evidence for apoptosis of murine macrophages by Actinobacillus actinomycetemcomitans infection. Infect Immun 63:3914–3919
    [Google Scholar]
  8. Kato S., Nakashima K., Inoue M., Tomioka J., Nonaka K., Nishihara T., Kowashi Y. 2000; Human epithelial cell death caused by Actinobacillus actinomycetemcomitans infection. J Med Microbiol 49:739–745
    [Google Scholar]
  9. Korostoff J., Wang J. F., Kieba I., Miller M., Shenker B. J., Lally E. T. 1998; Actinobacillus actinomycetemcomitans leukotoxin induces apoptosis in HL-60 cells. Infect Immun 66:4474–4483
    [Google Scholar]
  10. Kyriakis J. M., Avruch J. 2001; Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev 81:807–869
    [Google Scholar]
  11. Kyriakis J. M., Banerjee P., Nikolakaki E., Dai T., Rubie E. A., Ahmad M. F., Avruch J., Woodgett J. R. 1994; The stress-activated protein kinase subfamily of c-Jun kinases. Nature 369:156–160 [CrossRef]
    [Google Scholar]
  12. MacEwan D. J. 2002; TNF ligands and receptors – a matter of life and death. Br J Pharmacol 135:855–875 [CrossRef]
    [Google Scholar]
  13. Mangan D. F., Taichman N. S., Lally E. T., Wahl S. M. 1991; Lethal effects of Actinobacillus actinomycetemcomitans leukotoxin on human T lymphocytes. Infect Immun 59:3267–3272
    [Google Scholar]
  14. Mangan D. F., Mergenhagen S. E., Wahl S. M. 1993; Apoptosis in human monocytes: possible role in chronic inflammatory diseases. J Periodontol 64:461–466
    [Google Scholar]
  15. Molloy A., Laochumroonvorapong P., Kaplan G. 1994; Apoptosis, but not necrosis, of infected monocytes is coupled with killing of intracellular bacillus Calmette–Guerin. J Exp Med 180:1499–1509 [CrossRef]
    [Google Scholar]
  16. Muro M., Koseki T., Akifusa S., Kato S., Kowashi Y., Ohsaki Y., Yamato K., Nishijima M., Nishihara T. 1997; Role of CD14 molecules in internalization of Actinobacillus actinomycetemcomitans by macrophages and subsequent induction of apoptosis. Infect Immun 65:1147–1151
    [Google Scholar]
  17. Muro M., Nakashima K., Tomioka J., Kato S., Nonaka K., Yoshida T., Inoue M., Nishihara T., Kowashi Y. 1999; Inhibitory effect of lipopolysaccharide on apoptotic cell death in macrophages infected with Actinobacillus actinomycetemcomitans . FEMS Microbiol Lett 175:211–216 [CrossRef]
    [Google Scholar]
  18. Nagahira A., Nagahira K., Murafuji H., Abe K., Magota K., Matsui M., Oikawa S. 2001; Identification of a novel inhibitor of LPS-induced TNF-α production with antiproliferative activity in monocyte/macrophages. Biochem Biophys Res Commun 281:1030–1036 [CrossRef]
    [Google Scholar]
  19. Nakashima K., Tomioka J., Kato S., Nishihara T., Kowashi Y. 2002; Nitric oxide-mediated protection of A.actinomycetemcomitans -infected murine macrophages against apoptosis. Nitric Oxide 6:61–68 [CrossRef]
    [Google Scholar]
  20. Nalbant A., Zadeh H. H. 2002; Actinobacillus actinomycetemcomitans induces apoptosis of T lymphocytes by the Fas and Fas ligand pathway. Oral Microbiol Immunol 17:277–284 [CrossRef]
    [Google Scholar]
  21. Nonaka K., Ishisaki A., Muro M., Kato S., Oido M., Nakashima K., Kowashi Y., Nishihara T. 1998; Possible involvement of protein kinase C in apoptotic cell death of macrophages infected with Actinobacillus actinomycetemcomitans . FEMS Microbiol Lett 159:247–254 [CrossRef]
    [Google Scholar]
  22. Nonaka K., Ishisaki A., Okahashi N., Koseki T., Kato S., Muro M., Nakashima K., Nishihara T., Kowashi Y. 2001; Involvement of caspases in apoptotic cell death of murine macrophages infected with Actinobacillus actinomycetemcomitans . J Periodontal Res 36:40–47 [CrossRef]
    [Google Scholar]
  23. Oses-Prieto J. A., Lopez-Moratalla N., Santiago E., Jaffrezou J. P., Lopez-Zabalza M. J. 2000; Molecular mechanisms of apoptosis induced by an immunomodulating peptide on human monocytes. Arch Biochem Biophys 379:353–362 [CrossRef]
    [Google Scholar]
  24. Procyk K. J., Kovarik P., von Gabain A., Baccarini M. 1999; Salmonella typhimurium and lipopolysaccharide stimulate extracellularly regulated kinase activation in macrophages by a mechanism involving phosphatidylinositol 3-kinase and phospholipase D as novel intermediates. Infect Immun 67:1011–1017
    [Google Scholar]
  25. Shenker B. J., Hoffmaster R. H., Zekavat A., Yamaguchi N., Lally E. T., Demuth D. R. 2001; Induction of apoptosis in human T cells by Actinobacillus actinomycetemcomitans cytolethal distending toxin is a consequence of G2 arrest of the cell cycle. J Immunol 167:435–441 [CrossRef]
    [Google Scholar]
  26. Walker N. I., Harmon B. V., Gobe G. C., Kerr J. F. 1988; Patterns of cell death. Methods Achiev Exp Pathol 13:18–54
    [Google Scholar]
  27. Zychlinsky A., Sansonetti P. 1997; Perspectives series: host/pathogen interactions.Apoptosis in bacterial pathogenesis. J Clin Invest 100:493–495 [CrossRef]
    [Google Scholar]
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