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Alendronate regulates cytokine production induced by lipid A through nuclear factor-κB and Smad3 activation in human gingival fibroblasts.

Abstract：

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.

journal_name

J Periodontal Res

journal_title

Journal of periodontal research

authors

Tamai R,Sugiyama A,Kiyoura Y

doi

10.1111/j.1600-0765.2010.01302.x

subject

Has Abstract

pub_date

2011-02-01 00:00:00

pages

13-20

issue

1

eissn

0022-3484

issn

1600-0765

pii

JRE1302

journal_volume

46

pub_type

杂志文章

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