PMID- 20663020
OWN - NLM
STAT- MEDLINE
DCOM- 20110425
LR  - 20131121
IS  - 1600-0765 (Electronic)
IS  - 0022-3484 (Linking)
VI  - 46
IP  - 1
DP  - 2011 Feb
TI  - Alendronate regulates cytokine production induced by lipid A through nuclear 
      factor-kappaB and Smad3 activation in human gingival fibroblasts.
PG  - 13-20
LID - 10.1111/j.1600-0765.2010.01302.x [doi]
AB  - 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)-1beta, IL-6, 
      IL-8 and monocyte chemoattractant protein-1 (MCP-1) in culture supernatants were 
      measured by ELISA. We also examined nuclear factor-kappaB (NF-kappaB) 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-1beta 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-kappaB 
      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-kappaB and Smad3 
      activity.
CI  - (c) 2010 John Wiley & Sons A/S.
FAU - Tamai, R
AU  - Tamai R
AD  - Department of Oral Medical Science, Ohu University School of Dentistry, 31-1 
      Misumido, Tomitamachi, Koriyama, Fukushima, Japan.
FAU - Sugiyama, A
AU  - Sugiyama A
FAU - Kiyoura, Y
AU  - Kiyoura Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Periodontal Res
JT  - Journal of periodontal research
JID - 0055107
RN  - 0 (Bone Density Conservation Agents)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Interleukin-6)
RN  - 0 (Interleukin-8)
RN  - 0 (Lipid A)
RN  - 0 (NF-kappa B)
RN  - 0 (Smad3 Protein)
RN  - X1J18R4W8P (Alendronate)
SB  - IM
MH  - Alendronate/*pharmacology
MH  - Analysis of Variance
MH  - Bone Density Conservation Agents/*pharmacology
MH  - Cells, Cultured
MH  - Chemokine CCL2/biosynthesis/genetics
MH  - Cytokines/*biosynthesis/genetics
MH  - Fibroblasts/drug effects/immunology/metabolism
MH  - Gene Expression Regulation
MH  - Gingiva/cytology/*drug effects/metabolism
MH  - Humans
MH  - Interleukin-1beta/biosynthesis/genetics
MH  - Interleukin-6/biosynthesis/genetics
MH  - Interleukin-8/biosynthesis/genetics
MH  - Leukocytes, Mononuclear/drug effects/metabolism
MH  - Lipid A/immunology
MH  - NF-kappa B/*metabolism
MH  - Smad3 Protein/antagonists & inhibitors/*metabolism
MH  - Transcriptional Activation/*drug effects
EDAT- 2010/07/29 06:00
MHDA- 2011/04/26 06:00
CRDT- 2010/07/29 06:00
PHST- 2010/07/29 06:00 [entrez]
PHST- 2010/07/29 06:00 [pubmed]
PHST- 2011/04/26 06:00 [medline]
AID - JRE1302 [pii]
AID - 10.1111/j.1600-0765.2010.01302.x [doi]
PST - ppublish
SO  - J Periodontal Res. 2011 Feb;46(1):13-20. doi: 10.1111/j.1600-0765.2010.01302.x.