Reference - Detail
|Author||Yambe N, Tamai R, Mashima I, Kiyoura Y.|
|Title||Etidronate down-regulates Toll-like receptor 2 ligand-induced chemokine production by inhibiting MyD88 expression and NF-κB activation.|
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 Pam3Cys-Ser-(Lys)4 (Pam3CSK4, a TLR2 ligand) and lipid A (a TLR4 ligand).
METHODS:U937 cells were pretreated with or without etidronate, and then incubated with or without Pam3CSK4 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-κB (NF-κB) 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-κB p65 activation induced by Pam3CSK4, but not lipid A, in U937 cells. Etidronate also inhibited MyD88 expression in U937 cells incubated with Pam3CSK4.
CONCLUSION:Etidronate down-regulates IL-8 and MCP-1 production in U937 cells by inhibiting both the expression of MyD88 and activation of NF-κB p65 in the TLR2, but not TLR4, pathway.
|MeSH||Bone Density Conservation Agents / pharmacology* Chemokines / antagonists & inhibitors* Chemokines / metabolism Dose-Response Relationship, Drug Down-Regulation / drug effects Down-Regulation / physiology Etidronic Acid / pharmacology* Gene Expression Humans Ligands Myeloid Differentiation Factor 88 / antagonists & inhibitors* Myeloid Differentiation Factor 88 / biosynthesis NF-kappa B / antagonists & inhibitors* NF-kappa B / metabolism Toll-Like Receptor 2 / antagonists & inhibitors* Toll-Like Receptor 2 / metabolism U937 Cells|
|Human and Animal Cells||U937|