Alendronate augments interleukin-1beta release from macrophages infected with periodontal pathogenic bacteria through activation of caspase-1.
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.
Deng
Xue
X
Division of Oral Bacteriology, Department of Oral Medical Science, Ohu University School of Dentistry, 31-1 Misumido, Tomitamachi, Koriyama, Fukushima 963-8611, Japan.
Tamai
Riyoko
R
Endo
Yasuo
Y
Kiyoura
Yusuke
Y
D019386:Alendronate / Q000494:pharmacology*; D000818:Animals; D001438:Bacteroidaceae / Q000502:physiology*; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism*; D004002:Clodronic Acid / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D053583:Interleukin-1beta / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D010518:Periodontitis / Q000382:microbiology; D051193:Toll-Like Receptors
D050071:Bone Density Conservation Agents; D053583:Interleukin-1beta; D051193:Toll-Like Receptors; D004002:Clodronic Acid; D020170:Caspase 1; D019386:Alendronate