論文 - 詳細
| RRC ID | 66035 |
|---|---|
| 著者 | Hojo K, Tamai R, Kobayashi-Sakamoto M, Kiyoura Y. |
| タイトル | Etidronate down-regulates Toll-like receptor (TLR) 2 ligand-induced proinflammatory cytokine production by inhibiting NF-κB activation. |
| ジャーナル | Pharmacol Rep |
| Abstract |
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 Pam3Cys-Ser-(Lys)4 (Pam3CSK4, 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 Pam3CSK4 or lipid A for 24h. Levels of secreted interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-1α (MIP-1α) 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-κB (NF-κB) 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-α, MCP-1, and MIP-1α. Etidronate also inhibited Pam3CSK4-induced MCP-1 and TNF-α 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-κB but not p38 MAPK in J774.1 cells stimulated with Pam3CSK4 or lipid A. CONCLUSION:Etidronate likely inhibits proinflammatory cytokine production in J774.1 cells by suppressing NF-κB activation in the TLR2 and not the TLR4 pathway. |
| 巻・号 | 69(4) |
| ページ | 773-778 |
| 公開日 | 2017-8-1 |
| DOI | 10.1016/j.pharep.2017.03.009 |
| PII | S1734-1140(16)30355-3 |
| PMID | 28587938 |
| MeSH | Animals Bone Density Conservation Agents / pharmacology Cell Line Cytokines / genetics Cytokines / metabolism* Etidronic Acid / pharmacology* Gene Expression Regulation / drug effects* Humans Mice NF-kappa B / genetics NF-kappa B / metabolism* Toll-Like Receptor 2 / genetics Toll-Like Receptor 2 / metabolism* |
| IF | 2.761 |
| リソース情報 | |
| ヒト・動物細胞 | J774.1(RCB2652) THP-1(RCB1189) |