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Title: Alendronate augments interleukin-1{beta} release from macrophages infected with periodontal pathogenic bacteria through activation of caspase-1

Abstract

Nitrogen-containing bisphosphonates (NBPs) are anti-bone-resorptive drugs with inflammatory side effects that include osteomyelitis and osteonecrosis of the jaw. Oral bacteria have been considered to be a trigger for these NBP-associated jaw bone diseases. The present study examined the effects of alendronate (a typical NBP) and clodronate (a non-NBP) on the production of proinflammatory cytokines by macrophages infected with Porphyromonas gingivalis and Tannerella forsythia, which are important pathogens of periodontal diseases. Pretreatment with alendronate augmented IL-1{beta}, but not TNF{alpha}, production by macrophages infected with P. gingivalis or T. forsythia. This augmentation of IL-1{beta} production was inhibited by clodronate. Furthermore, caspase-1, a promoter of IL-1{beta} production, was activated by treatment with alendronate, and caspase-1 inhibitor reduced the production of IL-1{beta} induced by alendronate and P. gingivalis. These results suggest that NBPs augment periodontal pathogenic bacteria-induced IL-1{beta} release via caspase-1 activation, and this phenomenon may contribute to the development of NBP-associated inflammatory side effects including jaw osteomyelitis. Co-treatment with clodronate may prevent and/or reduce these inflammatory effects induced by NBPs.

Authors:
;  [1];  [2];  [3]
  1. Division of Oral Bacteriology, Department of Oral Medical Science, Ohu University School of Dentistry, 31-1 Misumido, Tomitamachi, Koriyama, Fukushima 963-8611 (Japan)
  2. Department of Molecular Regulation, Graduate School of Dentistry, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575 (Japan)
  3. Division of Oral Bacteriology, Department of Oral Medical Science, Ohu University School of Dentistry, 31-1 Misumido, Tomitamachi, Koriyama, Fukushima 963-8611 (Japan), E-mail: y-kiyoura@den.ohu-u.ac.jp
Publication Date:
OSTI Identifier:
21182736
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 235; Journal Issue: 1; Other Information: DOI: 10.1016/j.taap.2008.11.005; PII: S0041-008X(08)00481-X; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BACTERIA; DRUGS; INFLAMMATION; JAW; LIPIDS; LYMPHOKINES; MACROPHAGES; NITROGEN; OSTEOMYELITIS; PATHOGENS; PROMOTERS; SIDE EFFECTS

Citation Formats

Deng Xue, Tamai, Riyoko, Endo, Yasuo, and Kiyoura, Yusuke. Alendronate augments interleukin-1{beta} release from macrophages infected with periodontal pathogenic bacteria through activation of caspase-1. United States: N. p., 2009. Web. doi:10.1016/j.taap.2008.11.005.
Deng Xue, Tamai, Riyoko, Endo, Yasuo, & Kiyoura, Yusuke. Alendronate augments interleukin-1{beta} release from macrophages infected with periodontal pathogenic bacteria through activation of caspase-1. United States. doi:10.1016/j.taap.2008.11.005.
Deng Xue, Tamai, Riyoko, Endo, Yasuo, and Kiyoura, Yusuke. Sun . "Alendronate augments interleukin-1{beta} release from macrophages infected with periodontal pathogenic bacteria through activation of caspase-1". United States. doi:10.1016/j.taap.2008.11.005.
@article{osti_21182736,
title = {Alendronate augments interleukin-1{beta} release from macrophages infected with periodontal pathogenic bacteria through activation of caspase-1},
author = {Deng Xue and Tamai, Riyoko and Endo, Yasuo and Kiyoura, Yusuke},
abstractNote = {Nitrogen-containing bisphosphonates (NBPs) are anti-bone-resorptive drugs with inflammatory side effects that include osteomyelitis and osteonecrosis of the jaw. Oral bacteria have been considered to be a trigger for these NBP-associated jaw bone diseases. The present study examined the effects of alendronate (a typical NBP) and clodronate (a non-NBP) on the production of proinflammatory cytokines by macrophages infected with Porphyromonas gingivalis and Tannerella forsythia, which are important pathogens of periodontal diseases. Pretreatment with alendronate augmented IL-1{beta}, but not TNF{alpha}, production by macrophages infected with P. gingivalis or T. forsythia. This augmentation of IL-1{beta} production was inhibited by clodronate. Furthermore, caspase-1, a promoter of IL-1{beta} production, was activated by treatment with alendronate, and caspase-1 inhibitor reduced the production of IL-1{beta} induced by alendronate and P. gingivalis. These results suggest that NBPs augment periodontal pathogenic bacteria-induced IL-1{beta} release via caspase-1 activation, and this phenomenon may contribute to the development of NBP-associated inflammatory side effects including jaw osteomyelitis. Co-treatment with clodronate may prevent and/or reduce these inflammatory effects induced by NBPs.},
doi = {10.1016/j.taap.2008.11.005},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 1,
volume = 235,
place = {United States},
year = {2009},
month = {2}
}