This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Suzuki, T.
Right arrow Articles by Hasegawa, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Suzuki, T.
Right arrow Articles by Hasegawa, K.

 Previous Article  |  Next Article 

Infection and Immunity, April 2004, p. 1856-1865, Vol. 72, No. 4
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.4.1856-1865.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Mechanisms Involved in Apoptosis of Human Macrophages Induced by Lipopolysaccharide from Actinobacillus actinomycetemcomitans in the Presence of Cycloheximide

Takao Suzuki,1 Makoto Kobayashi,1* Kyoko Isatsu,1 Tatsuji Nishihara,2 Toshihiro Aiuchi,3 Kazuyasu Nakaya,3 and Kohji Hasegawa1

Department of Periodontology, Dental School,1 Laboratory of Biological Chemistry, School of Pharmaceutical Sciences, Showa University, Tokyo 145-8555,3 Department of Oral Microbiology, Kyushu Dental College, Fukuoka 803-8580, Japan2

Received 3 February 2003/ Returned for modification 30 April 2003/ Accepted 17 December 2003

Actinobacillus actinomycetemcomitans is a major periodontopathic bacterium with multiple virulence factors, including lipopolysaccharide (LPS). Previous reports have demonstrated that LPS induced apoptosis in a murine macrophage-like cell line, J744.1, as well as in peritoneal macrophages from C3H/HeN mice in the presence of cycloheximide (CHX). However, the detailed molecular mechanisms involved in the apoptosis of macrophages induced by LPS and CHX are not well known. To clarify the possible role of LPS in the induction of macrophage apoptosis, we investigated cell death induced by LPS from A. actinomycetemcomitans and CHX in human macrophage-like U937 cells, which were differentiated by 12-O-tetradecanoylphorbol 13-acetate (TPA), and also assessed the molecular mechanisms involved in the process. We found that TPA-differentiated U937 cells usually showed resistance to LPS-induced apoptosis. However, in the presence of CHX, LPS induced release of cytochrome c without modifying steady-state levels of Bcl-2, Bcl-xL, Bax, and Bak. Treatment with LPS in the presence of CHX also led to activation of caspase-3 and apoptosis via, in part, the CD14/toll-like receptor 4 (TLR4). The induction of cytochrome c release may have been due to dephosphorylation of Akt and Bad, which were cooperatively induced by CHX and LPS. However, endogenous tumor necrosis factor alpha- and Fas-induced signals, extracellular signal-regulated kinase kinase/mitogen-activated protein kinases and I-{kappa}B{alpha}/nuclear factor-{kappa}B (NF-{kappa}B) were not required for caspase-3-dependent apoptosis. These results emphasize the possible important role of the mitochondrial apoptotic pathway leading to caspase-3 activation in LPS-induced apoptosis of human macrophages in the presence of CHX.

* Corresponding author. Mailing address: Department of Periodontology, Showa University, Dental School, Kitasenzoku, Ohta-ku, Tokyo 145-8515, Japan. Phone: 81-3-3787-1151, ext. 354. Fax: 81-3-3787-9290. E-mail: perikoba{at}senzoku.showa-u.ac.jp.

Editor: V. J. DiRita

Infection and Immunity, April 2004, p. 1856-1865, Vol. 72, No. 4
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.4.1856-1865.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Xu, Y., Kim, S. O., Li, Y., Han, J. (2006). Autophagy Contributes to Caspase-independent Macrophage Cell Death. J. Biol. Chem. 281: 19179-19187 [Abstract] [Full Text]  
  • Mitchell, J. W., Baik, N., Castellino, F. J., Miles, L. A. (2006). Plasminogen inhibits TNF{alpha}-induced apoptosis in monocytes. Blood 107: 4383-4390 [Abstract] [Full Text]  
  • Ma, Y., Temkin, V., Liu, H., Pope, R. M. (2005). NF-{kappa}B Protects Macrophages from Lipopolysaccharide-induced Cell Death: THE ROLE OF CASPASE 8 AND RECEPTOR-INTERACTING PROTEIN. J. Biol. Chem. 280: 41827-41834 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»