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Infection and Immunity, March 2004, p. 1318-1325, Vol. 72, No. 3
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.3.1318-1325.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Biological Activities of Bacteroides forsythus Lipoproteins and Their Possible Pathological Roles in Periodontal Disease

Akira Hasebe,1 Atsutoshi Yoshimura,2 Takeshi Into,1 Hideo Kataoka,1 Saori Tanaka,3 Shinichi Arakawa,4,5 Hiroaki Ishikura,4,5 Douglas T. Golenbock,6 Tsutomu Sugaya,2 Nobuo Tsuchida,4 Masamitsu Kawanami,3 Yoshitaka Hara,2 and Ken-ichiro Shibata1*

Departments of Oral Pathobiological Science,1 Oral Health Science, Hokkaido University Graduate School of Dental Medicine, Nishi 7, Kita 13, Kita-ku, Sapporo 060-8586, Division of Periodontology,3 Department of Developmental and Reconstructive Medicine, Course of Medical and Dental Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8588,2 Department of Molecular Cellular Oncology and Microbiology,4 Department of Periodontology,5 Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-Ku, Tokyo 113-8549, Japan, and Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts 016056

Received 6 October 2003/ Returned for modification 15 November 2003/ Accepted 8 December 2003

Bacteroides forsythus is a gram-negative, anaerobic, fusiform bacterium and is considered to be an etiological agent in periodontal disease. A lipoprotein fraction prepared from B. forsythus cells by Triton X-114 phase separation (BfLP) activated human gingival fibroblasts and a human monocytic cell line, THP-1, to induce interleukin-6 production and tumor necrosis factor alpha production. BfLP was found to be capable of inducing nuclear factor-{kappa}B translocation in human gingival fibroblasts and THP-1 cells. By using Chinese hamster ovary K1 cells transfected with Toll-like receptor genes together with a nuclear factor-{kappa}B-dependent CD25 reporter plasmid, it was found that signaling by BfLP was mediated by Toll-like receptor 2 but not by CD14 or Toll-like receptor 4. BfLP induced apoptotic cell death in human gingival fibroblasts, KB cells (an oral epithelial cell line), HL-60 cells (a human myeloid leukemia cell line), and THP-1 cells but not in MOLT4 cells (a T-cell leukemia cell line). Caspase-8, an initiator caspase in apoptosis, was found to be activated in these cells in response to BfLP stimulation. Thus, this study suggested that BfLP plays some etiological roles in oral infections, especially periodontal disease, by induction of cell activation or apoptosis.


* Corresponding author. Mailing address: Department of Oral Pathobiological Science, Hokkaido University Graduate School of Dental Medicine, Nishi 7, Kita 13, Kita-ku, Sapporo 060-8586, Japan. Phone: 81-11-706 4240. Fax: 81-11-706 4901. E-mail: shibaken{at}den.hokudai.ac.jp.

Editor: J. B. Bliska


Infection and Immunity, March 2004, p. 1318-1325, Vol. 72, No. 3
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.3.1318-1325.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.




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