PMID- 19501197
OWN - NLM
STAT- MEDLINE
DCOM- 20100114
LR  - 20131121
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 9
IP  - 9
DP  - 2009 Aug
TI  - Mouse macrophages primed with alendronate down-regulate monocyte chemoattractant 
      protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha) 
      production in response to Toll-like receptor (TLR) 2 and TLR4 agonist via Smad3 
      activation.
PG  - 1115-21
LID - 10.1016/j.intimp.2009.05.010 [doi]
AB  - Alendronate is one of the nitrogen-containing bisphosphonates (NBPs) used as 
      anti-bone resorptive drugs. However, NBPs have inflammatory side effects 
      including osteomyelitis and osteonecrosis of the jaw. In the present study, we 
      examined the effects of alendronate on chemokine production by the 
      macrophage-like cell line, J774.1, when incubated with Pam(3)CSK(4) (a Toll-like 
      receptor (TLR) 2 agonist) and Lipid A (a TLR4 agonist). Pretreatment of J774.1 
      cells with alendronate decreased the production of TLR ligand-induced monocyte 
      chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1alpha 
      (MIP-1alpha) but did not influence nuclear factor-kappaB (NF-kappaB) activation. 
      While this agent induced caspase-8 activation, a caspase-8 inhibitor did not 
      affect the decrease in MCP-1 production by alendronate and TLR ligands. Thus, the 
      alendronate-mediated decrease in chemokine production was independent of 
      NF-kappaB and caspase-8 activation. Although transforming growth factor-beta1 
      (TGF-beta1) is known to inhibit chemokine production by various cell types via 
      Smad3 activation, pretreatment with alendronate did not increase TGF-beta1 
      production by J774.1 cells incubated in the presence or absence of TLR ligands. 
      However, alendronate directly activated Smad3. These results suggest that by 
      down-regulating MCP-1 and MIP-1alpha production via Smad3, long-term use of 
      alendronate might inhibit normal activation and migration of osteoclasts and 
      cause osteonecrosis.
FAU - Masuda, Takahiro
AU  - Masuda T
AD  - Department of Endodontics and Periodontics, Ohu University Graduate School of 
      Dentistry, Misumido, Tomitamachi, Koriyama, Fukushima, Japan.
FAU - Deng, Xue
AU  - Deng X
FAU - Tamai, Riyoko
AU  - Tamai R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090606
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Chemokine CCL2)
RN  - 0 (Lipid A)
RN  - 0 (Lipopeptides)
RN  - 0 (Macrophage Inflammatory Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Pam(3)CSK(4) peptide)
RN  - 0 (Smad3 Protein)
RN  - 0 (Smad3 protein, mouse)
RN  - 0 (Tlr2 protein, mouse)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptor 4)
RN  - X1J18R4W8P (Alendronate)
SB  - IM
MH  - Alendronate/*pharmacology/therapeutic use
MH  - Animals
MH  - Bone Resorption/drug therapy
MH  - Cell Line
MH  - Chemokine CCL2/genetics/immunology/*metabolism
MH  - Down-Regulation
MH  - Lipid A/pharmacology
MH  - Lipopeptides/pharmacology
MH  - Macrophage Activation/drug effects
MH  - Macrophage Inflammatory Proteins/genetics/immunology/*metabolism
MH  - Macrophages/drug effects/immunology/*metabolism/pathology
MH  - Mice
MH  - NF-kappa B/metabolism
MH  - Smad3 Protein/genetics/immunology/*metabolism
MH  - Toll-Like Receptor 2/agonists
MH  - Toll-Like Receptor 4/agonists
MH  - Transcriptional Activation/drug effects
EDAT- 2009/06/09 09:00
MHDA- 2010/01/15 06:00
CRDT- 2009/06/09 09:00
PHST- 2009/03/02 00:00 [received]
PHST- 2009/05/28 00:00 [revised]
PHST- 2009/05/28 00:00 [accepted]
PHST- 2009/06/09 09:00 [entrez]
PHST- 2009/06/09 09:00 [pubmed]
PHST- 2010/01/15 06:00 [medline]
AID - S1567-5769(09)00193-3 [pii]
AID - 10.1016/j.intimp.2009.05.010 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2009 Aug;9(9):1115-21. doi: 10.1016/j.intimp.2009.05.010. 
      Epub 2009 Jun 6.