PMID- 33251898
OWN - NLM
STAT- MEDLINE
DCOM- 20210923
LR  - 20210923
IS  - 1532-2513 (Electronic)
IS  - 0892-3973 (Linking)
VI  - 43
IP  - 1
DP  - 2021 Feb
TI  - Etidronate down-regulates Toll-like receptor 2 ligand-induced chemokine 
      production by inhibiting MyD88 expression and NF-kappaB activation.
PG  - 51-57
LID - 10.1080/08923973.2020.1850761 [doi]
AB  - OBJECTIVE: Pretreatment of J774.1 cells with etidronate, a 
      non-nitrogen-containing bisphosphonate (non-NBP) used as an antibone resorptive 
      drug, was previously reported to inhibit Toll-like receptor (TLR) 2 
      agonist-induced proinflammatory cytokine production. The present study aimed to 
      examine the effects of etidronate on chemokine production by human monocytic U937 
      cells incubated with Pam(3)Cys-Ser-(Lys)(4) (Pam(3)CSK(4), a TLR2 ligand) and 
      lipid A (a TLR4 ligand). METHODS: U937 cells were pretreated with or without 
      etidronate, and then incubated with or without Pam(3)CSK(4) or lipid A. Levels of 
      secreted human interleukin (IL)-8 and monocyte chemoattractant protein-1 (MCP-1) 
      in culture supernatants and activation of nuclear factor-kappaB (NF-kappaB) p65 were 
      measured by enzyme-linked immunosorbent assay (ELISA). Cytotoxicity was 
      determined by measuring lactate dehydrogenase (LDH) activity in supernatants. 
      Expression of intracellular adhesion molecule (ICAM)-1 and MyD88 was analyzed by 
      flow cytometry and Western blot analysis, respectively. RESULTS: Etidronate 
      down-regulated IL-8 and MCP-1 production and NF-kappaB p65 activation induced by 
      Pam(3)CSK(4,) but not lipid A, in U937 cells. Etidronate also inhibited MyD88 
      expression in U937 cells incubated with Pam(3)CSK(4). CONCLUSION: Etidronate 
      down-regulates IL-8 and MCP-1 production in U937 cells by inhibiting both the 
      expression of MyD88 and activation of NF-kappaB p65 in the TLR2, but not TLR4, 
      pathway.
FAU - Yambe, Naohito
AU  - Yambe N
AD  - Department of Infectious Diseases, Ohu University Graduate School of Dentistry, 
      Koriyama, Japan.
FAU - Tamai, Riyoko
AU  - Tamai R
AUID- ORCID: 0000-0002-2782-2763
AD  - Department of Infectious Diseases, Ohu University Graduate School of Dentistry, 
      Koriyama, Japan.
AD  - Department of Oral Medical Science, Ohu University School of Dentistry, Koriyama, 
      Japan.
FAU - Mashima, Izumi
AU  - Mashima I
AD  - Department of Oral Medical Science, Ohu University School of Dentistry, Koriyama, 
      Japan.
FAU - Kiyoura, Yusuke
AU  - Kiyoura Y
AD  - Department of Infectious Diseases, Ohu University Graduate School of Dentistry, 
      Koriyama, Japan.
AD  - Department of Oral Medical Science, Ohu University School of Dentistry, Koriyama, 
      Japan.
LA  - eng
PT  - Journal Article
DEP - 20201129
PL  - England
TA  - Immunopharmacol Immunotoxicol
JT  - Immunopharmacology and immunotoxicology
JID - 8800150
RN  - 0 (Bone Density Conservation Agents)
RN  - 0 (Chemokines)
RN  - 0 (Ligands)
RN  - 0 (MYD88 protein, human)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (NF-kappa B)
RN  - 0 (TLR2 protein, human)
RN  - 0 (Toll-Like Receptor 2)
RN  - M2F465ROXU (Etidronic Acid)
SB  - IM
MH  - Bone Density Conservation Agents/*pharmacology
MH  - Chemokines/*antagonists & inhibitors/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Down-Regulation/drug effects/physiology
MH  - Etidronic Acid/*pharmacology
MH  - Gene Expression
MH  - Humans
MH  - Ligands
MH  - Myeloid Differentiation Factor 88/*antagonists & inhibitors/biosynthesis
MH  - NF-kappa B/*antagonists & inhibitors/metabolism
MH  - Toll-Like Receptor 2/*antagonists & inhibitors/metabolism
MH  - U937 Cells
OTO - NOTNLM
OT  - NF-kappaB
OT  - Non-NBP
OT  - TLR
OT  - chemokines
OT  - etidronate
OT  - myeloid differentiation factor 88 (MyD88)
EDAT- 2020/12/01 06:00
MHDA- 2021/09/24 06:00
CRDT- 2020/11/30 08:40
PHST- 2020/12/01 06:00 [pubmed]
PHST- 2021/09/24 06:00 [medline]
PHST- 2020/11/30 08:40 [entrez]
AID - 10.1080/08923973.2020.1850761 [doi]
PST - ppublish
SO  - Immunopharmacol Immunotoxicol. 2021 Feb;43(1):51-57. doi: 
      10.1080/08923973.2020.1850761. Epub 2020 Nov 29.