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Alendronate regulates cytokine production induced by lipid A through nuclear factor-κB and Smad3 activation in human gingival fibroblasts.
MedLine Citation:
PMID:  20663020     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
BACKGROUND AND OBJECTIVE: Nitrogen-containing bisphosphonates (NBPs) are widely used as anti-bone-resorptive drugs. However, use of NBPs results in inflammatory side-effects, including jaw osteomyelitis. In the present study, we examined the effects of alendronate, a typical NBP, on cytokine production by human peripheral blood mononuclear cells (PBMCs) and gingival fibroblasts incubated with lipid A.
METHODS: The PBMCs and gingival fibroblasts were pretreated with or without alendronate for 24 h. Cells were then incubated in the presence or absence of lipid A for a further 24 h. Levels of secreted human interleukin (IL)-1β, IL-6, IL-8 and monocyte chemoattractant protein-1 (MCP-1) in culture supernatants were measured by ELISA. We also examined nuclear factor-κB (NF-κB) activation in both types of cells by ELISA. Activation of Smad3 in the cells was assessed by flow cytometry. In addition, we performed an inhibition assay using SIS3, a specific inhibitor for Smad3.
RESULTS: Pretreatment of PBMCs with alendronate promoted lipid A-induced production of IL-1β and IL-6, but decreased lipid A-induced IL-8 and MCP-1 production. In human gingival fibroblasts, alendronate pretreatment increased lipid A-induced production of IL-6 and IL-8, and increased NF-κB activation in gingival fibroblasts but not PBMCs stimulated with lipid A. In contrast, alendronate activated Smad3 in both types of cells. Finally, SIS3 inhibited alendronate-augmented IL-6 and IL-8 production by human gingival fibroblasts but up-regulated alendronate-decreased IL-8 production by PBMCs.
CONCLUSION: These results suggest that alendronate-mediated changes in cytokine production by gingival fibroblasts occur via regulation of NF-κB and Smad3 activity.
Authors:
R Tamai; A Sugiyama; Y Kiyoura
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of periodontal research     Volume:  46     ISSN:  1600-0765     ISO Abbreviation:  J. Periodont. Res.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-06     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0055107     Medline TA:  J Periodontal Res     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  13-20     Citation Subset:  D; IM    
Copyright Information:
© 2010 John Wiley & Sons A/S.
Affiliation:
Department of Oral Medical Science, Ohu University School of Dentistry, 31-1 Misumido, Tomitamachi, Koriyama, Fukushima, Japan.
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