| Alendronate regulates cytokine production induced by lipid A through nuclear factor-κB and Smad3 activation in human gingival fibroblasts. | |
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MedLine Citation:
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PMID: 20663020 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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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. |
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Authors:
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R Tamai; A Sugiyama; Y Kiyoura |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of periodontal research Volume: 46 ISSN: 1600-0765 ISO Abbreviation: J. Periodont. Res. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-06 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0055107 Medline TA: J Periodontal Res Country: Denmark |
Other Details:
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Languages: eng Pagination: 13-20 Citation Subset: D; IM |
Copyright Information:
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© 2010 John Wiley & Sons A/S. |
Affiliation:
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Department of Oral Medical Science, Ohu University School of Dentistry, 31-1 Misumido, Tomitamachi, Koriyama, Fukushima, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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