Alendronate augments interleukin-1beta release from macrophages infected with periodontal pathogenic bacteria through activation of caspase-1.
Toxicol Appl Pharmacol
; 235(1): 97-104, 2009 Feb 15.
Article
in En
| MEDLINE
| ID: mdl-19063908
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-1beta, but not TNFalpha, production by macrophages infected with P. gingivalis or T. forsythia. This augmentation of IL-1beta production was inhibited by clodronate. Furthermore, caspase-1, a promoter of IL-1beta production, was activated by treatment with alendronate, and caspase-1 inhibitor reduced the production of IL-1beta induced by alendronate and P. gingivalis. These results suggest that NBPs augment periodontal pathogenic bacteria-induced IL-1beta 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Bacteroidaceae
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Alendronate
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Caspase 1
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Bone Density Conservation Agents
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Interleukin-1beta
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Macrophages
Limits:
Animals
Language:
En
Journal:
Toxicol Appl Pharmacol
Year:
2009
Document type:
Article
Affiliation country:
Japan