姜黄素通过抑制核因子-κB 信号通路介导 Nod 样受体 3 炎性小体减轻尿酸单钠诱导的痛风性关节炎。

Curcumin ameliorates monosodium urate-induced gouty arthritis through Nod-like receptor 3 inflammasome mediation via inhibiting nuclear factor-kappa B signaling.

机构信息

Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, China.

Department of Orthopedics, Yongzhou Central Hospital, Yongzhou, China.

出版信息

J Cell Biochem. 2019 Apr;120(4):6718-6728. doi: 10.1002/jcb.27969. Epub 2018 Dec 28.

DOI:10.1002/jcb.27969

PMID:30592318

Abstract

BACKGROUND

Monosodium urate (MSU) crystals-induced inflammation is a key initiator in gouty arthritis. Curcumin is an active ingredient possessing anti-inflammatory efficacy. But the underlying mechanism is not fully understood and its effect on gouty arthritis remains elusive.

METHODS

We evaluated the effects of curcumin on cell viability in primary rat abdominal macrophages with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). Then supernatants of MSU crystals-stimulated cells were collected and subjected to enzyme-linked immunosorbent assay for checking the modulation of curcumin on interleukin (IL)-1β and tumor necrosis factor (TNF)-α. Meanwhile, cells were analyzed by using Western blot analysis and quantitative polymerase chain reaction (QPCR) to investigate the effects of curcumin on Nod-like receptor 3 (NLRP3) inflammasome/nuclear factor-kappa B (NF-κB) signaling. We also investigated the in vivo efficacy of curcumin with MSU-induced gouty arthritis rat models.

RESULTS

Curcumin could reduce MSU crystals-induced IL-1β and TNF-α in vitro. Western blot analysis and QPCR results revealed that curcumin regulated the production of these cytokines by suppressing the expression of inflammasome key components, including NLRP3, caspase-1. Further studies showed that the suppressive efficacy of curcumin on inflammasome was mediated by inhibiting MSU-induced NF-κB signaling activation. Intraperitoneal administration of curcumin could ameliorate symptoms of MSU-induced gouty arthritis, including the joint circumference, infiltration of neutrophils in knee joints, and production of IL-1β, TNF-α, and elastase. Western blot analysis revealed that the levels of NLRP3, procaspase-1, caspase-1, pro-IL-1β, and IL-1β were downregulated by curcumin in vivo.

CONCLUSIONS

These results indicated that curcumin could effectively ameliorate MSU crystal-induced gouty arthritis through NLRP3 inflammasome mediation via inhibiting NF-κB signaling both in vitro and in vivo, suggesting a promising active ingredient for the prevention and treatment of gouty arthritis.

摘要

背景

单钠尿酸盐（MSU）晶体诱导的炎症是痛风性关节炎的一个关键启动因素。姜黄素是一种具有抗炎功效的活性成分。但其中的作用机制尚不完全清楚，其对痛风性关节炎的疗效仍不明确。

方法

我们用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）评估姜黄素对原代大鼠腹腔巨噬细胞活力的影响。然后收集 MSU 晶体刺激细胞的上清液，用酶联免疫吸附试验（ELISA）检测姜黄素对白细胞介素（IL）-1β和肿瘤坏死因子（TNF）-α的调节作用。同时，用 Western blot 分析和定量聚合酶链反应（QPCR）分析姜黄素对 Nod-like receptor 3（NLRP3）炎症小体/核因子-κB（NF-κB）信号的影响。我们还利用 MSU 诱导的痛风性关节炎大鼠模型研究了姜黄素的体内疗效。

结果

姜黄素可减少 MSU 晶体诱导的体外 IL-1β和 TNF-α。Western blot 分析和 QPCR 结果表明，姜黄素通过抑制炎症小体关键成分（包括 NLRP3、caspase-1）的表达来调节这些细胞因子的产生。进一步的研究表明，姜黄素对炎症小体的抑制作用是通过抑制 MSU 诱导的 NF-κB 信号激活来介导的。腹腔内给予姜黄素可改善 MSU 诱导的痛风性关节炎的症状，包括关节周长、膝关节中性粒细胞浸润以及 IL-1β、TNF-α 和弹性蛋白酶的产生。Western blot 分析表明，姜黄素可下调体内 NLRP3、原 Caspase-1、Caspase-1、Pro-IL-1β 和 IL-1β 的水平。