Etidronate down-regulates Toll-like receptor 2 ligand-induced chemokine production by inhibiting MyD88 expression and NF-κB activation,Immunopharmacology and Immunotoxicology

当前位置： X-MOL 学术 › Immunopharmacol. Immunotoxicol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Etidronate down-regulates Toll-like receptor 2 ligand-induced chemokine production by inhibiting MyD88 expression and NF-κB activation
Immunopharmacology and Immunotoxicology ( IF 2.9 ) Pub Date : 2020-11-29 , DOI: 10.1080/08923973.2020.1850761
Naohito Yambe ₁ , Riyoko Tamai _{1,

2} , Izumi Mashima ₂ , Yusuke Kiyoura _{1,

2}

Affiliation

Abstract

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 Pam₃CSK_4, 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.

中文翻译：

Etidronate 通过抑制 MyD88 表达和 NF-κB 激活下调 Toll 样受体 2 配体诱导的趋化因子产生

摘要

客观的

J774.1 细胞用依替膦酸盐预处理，一种不含氮的双膦酸盐 (non-NBP)，用作抗骨吸收药物，以前据报道可抑制 Toll 样受体 (TLR) 2 激动剂诱导的促炎细胞因子产生。本研究旨在检查依替膦酸盐对与 Pam ₃ Cys-Ser-(Lys) ₄（Pam ₃ CSK ₄，一种 TLR2 配体）和脂质 A（一种 TLR4 配体）一起孵育的人单核细胞 U937 细胞产生趋化因子的影响。

方法

U937 细胞用或不用依替膦酸盐预处理，然后用或不用 Pam ₃ CSK ₄或脂质 A孵育。培养上清液中分泌的人白细胞介素 (IL)-8 和单核细胞趋化蛋白-1 (MCP-1) 的水平和核因子-κB (NF-κB) p65 通过酶联免疫吸附测定 (ELISA) 进行测量。通过测量上清液中的乳酸脱氢酶 (LDH) 活性来确定细胞毒性。分别通过流式细胞术和蛋白质印迹分析来分析细胞内粘附分子(ICAM)-1和MyD88的表达。