PMID- 28587938
OWN - NLM
STAT- MEDLINE
DCOM- 20180509
LR  - 20200106
IS  - 2299-5684 (Electronic)
IS  - 1734-1140 (Linking)
VI  - 69
IP  - 4
DP  - 2017 Aug
TI  - Etidronate down-regulates Toll-like receptor (TLR) 2 ligand-induced 
      proinflammatory cytokine production by inhibiting NF-kappaB activation.
PG  - 773-778
LID - S1734-1140(16)30355-3 [pii]
LID - 10.1016/j.pharep.2017.03.009 [doi]
AB  - BACKGROUND: Etidronate is a non-nitrogen-containing bisphosphonate (non-NBP) used 
      for anti-bone resorptive therapy as well as having inhibitory effects on 
      atherosclerotic plaques. The present study examined the effects of etidronate on 
      the production of proinflammatory cytokines and chemokines by the macrophage-like 
      cell line, J774.1, incubated with Pam(3)Cys-Ser-(Lys)(4) (Pam(3)CSK(4), a 
      Toll-like receptor (TLR) 2 agonist) and lipid A (a TLR4 agonist). METHODS: J774.1 
      cells and human monocytic THP-1 cells were pretreated with or without etidronate 
      for 5min, and then incubated with or without Pam(3)CSK(4) or lipid A for 24h. 
      Levels of secreted interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), 
      monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory 
      protein-1alpha (MIP-1alpha) in culture supernatants were measured by enzyme-linked 
      immunosorbent assay (ELISA). Cytotoxicity was determined by LDH activity in the 
      supernatants. We also examined the effects of etidronate on the activation of 
      nuclear factor-kappaB (NF-kappaB) and p38 mitogen-activated protein kinase (MAPK) in 
      J774.1 cells by ELISA and Western blotting. RESULTS: Treatment of J774.1 cells 
      with etidronate down-regulated TLR2 ligand-induced production of IL-6, TNF-alpha, 
      MCP-1, and MIP-1alpha. Etidronate also inhibited Pam(3)CSK(4)-induced MCP-1 and TNF-alpha 
      production by THP-1 cells. However, etidronate did not induce cytotoxicity and 
      reduced lipid A-induced cytotoxicity in J774.1 cells. In addition, this agent did 
      not down-regulate TLR4 ligand-induced proinflammatory cytokine production. 
      Furthermore, etidronate inhibited the translocation of NF-kappaB but not p38 MAPK in 
      J774.1 cells stimulated with Pam(3)CSK(4) or lipid A. CONCLUSION: Etidronate 
      likely inhibits proinflammatory cytokine production in J774.1 cells by 
      suppressing NF-kappaB activation in the TLR2 and not the TLR4 pathway.
CI  - Copyright (c) 2017 Institute of Pharmacology, Polish Academy of Sciences. Published 
      by Elsevier Urban & Partner Sp. z o.o. All rights reserved.
FAU - Hojo, Kentaro
AU  - Hojo K
AD  - Department of Infectious Diseases, Ohu University Graduate School of Dentistry, 
      31-1 Misumido, Tomitamachi, Koriyama, Fukushima 963-8611, Japan.
FAU - Tamai, Riyoko
AU  - Tamai R
AD  - Department of Infectious Diseases, Ohu University Graduate School of Dentistry, 
      31-1 Misumido, Tomitamachi, Koriyama, Fukushima 963-8611, Japan; Department of 
      Oral Medical Science, Ohu University School of Dentistry, 31-1 Misumido, 
      Tomitamachi, Koriyama, Fukushima 963-8611, Japan. Electronic address: 
      r-tamai@den.ohu-u.ac.jp.
FAU - Kobayashi-Sakamoto, Michiyo
AU  - Kobayashi-Sakamoto M
AD  - Department of Oral Medical Science, Ohu University School of Dentistry, 31-1 
      Misumido, Tomitamachi, Koriyama, Fukushima 963-8611, Japan.
FAU - Kiyoura, Yusuke
AU  - Kiyoura Y
AD  - Department of Infectious Diseases, Ohu University Graduate School of Dentistry, 
      31-1 Misumido, Tomitamachi, Koriyama, Fukushima 963-8611, Japan; Department of 
      Oral Medical Science, Ohu University School of Dentistry, 31-1 Misumido, 
      Tomitamachi, Koriyama, Fukushima 963-8611, Japan.
LA  - eng
PT  - Journal Article
DEP - 20170319
PL  - Switzerland
TA  - Pharmacol Rep
JT  - Pharmacological reports : PR
JID - 101234999
RN  - 0 (Bone Density Conservation Agents)
RN  - 0 (Cytokines)
RN  - 0 (NF-kappa B)
RN  - 0 (TLR2 protein, human)
RN  - 0 (Tlr2 protein, mouse)
RN  - 0 (Toll-Like Receptor 2)
RN  - M2F465ROXU (Etidronic Acid)
SB  - IM
MH  - Animals
MH  - Bone Density Conservation Agents/pharmacology
MH  - Cell Line
MH  - Cytokines/genetics/*metabolism
MH  - Etidronic Acid/*pharmacology
MH  - Gene Expression Regulation/*drug effects
MH  - Humans
MH  - Mice
MH  - NF-kappa B/genetics/*metabolism
MH  - Toll-Like Receptor 2/genetics/*metabolism
OTO - NOTNLM
OT  - Etidronate
OT  - NF-kappaB
OT  - Non-NBPs
OT  - Proinflammatory cytokines
OT  - TLR
EDAT- 2017/06/08 06:00
MHDA- 2018/05/10 06:00
CRDT- 2017/06/08 06:00
PHST- 2016/11/10 00:00 [received]
PHST- 2017/02/14 00:00 [revised]
PHST- 2017/03/15 00:00 [accepted]
PHST- 2017/06/08 06:00 [pubmed]
PHST- 2018/05/10 06:00 [medline]
PHST- 2017/06/08 06:00 [entrez]
AID - S1734-1140(16)30355-3 [pii]
AID - 10.1016/j.pharep.2017.03.009 [doi]
PST - ppublish
SO  - Pharmacol Rep. 2017 Aug;69(4):773-778. doi: 10.1016/j.pharep.2017.03.009. Epub 
      2017 Mar 19.