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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 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.



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。

结果

Etidronate在 U937 细胞中下调 Pam 3 CSK 4而非脂质 A诱导的 IL-8 和 MCP-1 产生和 NF-κB p65 活化。Etidronate 还抑制了与 Pam 3 CSK 4孵育的 U937 细胞中 MyD88 的表达。

结论

Etidronate 通过抑制 TLR2(而非 TLR4)途径中 MyD88 的表达和 NF-κB p65 的激活,下调 U937 细胞中 IL-8 和 MCP-1 的产生。

更新日期:2021-01-19
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