Actinobacillus actinomycetemcomitans induces apoptosis in human monocytic THP-1 cells

Satsuki Kato1, Norihiko Sugimura1, Keisuke Nakashima1

  • 1Department of Periodontology and Endodontology, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan 2Department of Oral Microbiology, Kyusyu Dental College, Fukuoka 803-8580, Japan.

Insights

Actinobacillus actinomycetemcomitans infection triggers apoptosis in human immune cells, involving p38 MAPK and tumor necrosis factor alpha. This process may contribute to periodontal disease progression.

Area of Science:

  • Immunology
  • Cell Biology
  • Microbiology

Background:

  • Actinobacillus actinomycetemcomitans infection induces apoptosis in specific cell lines.
  • Mitogen-activated protein kinase (MAPK) family members regulate apoptosis.
  • MAPK signaling pathways are crucial in cellular responses to stress and growth factors.

Purpose of the Study:

  • To determine if human immune cells undergo apoptosis upon A. actinomycetemcomitans infection.
  • To investigate the involvement of the MAPK family in this apoptotic process.

Main Methods:

  • Human monocytic THP-1 cells were infected with A. actinomycetemcomitans.
  • Apoptosis was assessed by monitoring lactate dehydrogenase release and DNA fragmentation.
  • Agarose gel electrophoresis was used to confirm DNA fragmentation patterns.
  • p38 MAPK activity and tumor necrosis factor alpha (TNF-alpha) levels were measured.
  • The effects of a p38 inhibitor and an anti-TNF-alpha antibody were evaluated.

Main Results:

  • A. actinomycetemcomitans infection induced apoptosis in THP-1 cells, evidenced by DNA fragmentation.
  • p38 MAPK activity and TNF-alpha levels increased post-infection.
  • Inhibition of p38 MAPK or TNF-alpha reduced cell death and TNF-alpha levels.
  • Exogenous TNF-alpha did not induce apoptosis in uninfected cells.
  • Anti-TNF-alpha antibody decreased p38 MAPK activity.

Conclusions:

  • A. actinomycetemcomitans infection causes apoptosis in human immune cells (THP-1).
  • p38 MAPK is directly involved in mediating this apoptosis.
  • TNF-alpha appears to play an indirect role, potentially by enhancing p38 MAPK activity.
  • This A. actinomycetemcomitans-induced apoptosis may be significant in the initiation and progression of periodontal diseases.

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