Curcumin attenuates lupus nephritis by inhibiting neutrophil migration via PI3K/AKT/NF-κB signalling pathway.

IF 3.7 2区 医学 Q1 RHEUMATOLOGY Lupus Science & Medicine Pub Date : 2024-07-24 DOI:10.1136/lupus-2024-001220
Hui Yang, Haiwei Zhang, Lili Tian, Panpan Guo, Shanshan Liu, Hongwei Chen, Lingyun Sun
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Abstract

Objective: To investigate the role of curcumin in the treatment of lupus nephritis (LN) by inhibiting the migration of neutrophils and the underlying mechanism involved.

Methods: Two lupus mouse models, MRL/lpr mice and R848-treated mice, were treated with 50 mg/kg curcumin by intraperitoneal injection. H&E and Masson staining were used to estimate histopathological changes in the kidney. Immunofluorescence was used to assess the deposition of immune complexes. The expression of inflammatory factors was detected by enzyme-linked immunosorbent assay (ELISA) and real-time reverse transcription polymerase reaction (RT-PCR), and the protein expression was detected by western blotting.

Results: We revealed the remarkable potential of curcumin in improving inflammatory conditions in both MRL/lpr mice and R848-induced lupus mice. Curcumin effectively decelerates the progression of inflammation and diminishes the infiltration of neutrophils and their release of pivotal inflammatory factors, thereby reducing inflammation in renal tissues. Mechanistically, curcumin significantly inhibits the expression of p-PI3K, p-AKT and p-NF-κB, which are upregulated by interleukin-8 to induce neutrophil migration and renal inflammation, thereby reducing neutrophil migration and the release of inflammatory factors.

Conclusion: Curcumin significantly inhibits the recruitment of neutrophils and the release of proinflammatory factors in the kidney by inhibiting the PI3K/AKT/NF-κB signalling pathway, providing new therapeutic targets and medication strategies for the treatment of LN.

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姜黄素通过 PI3K/AKT/NF-κB 信号通路抑制中性粒细胞迁移,从而减轻狼疮肾炎。
目的:研究姜黄素通过抑制中性粒细胞迁移治疗狼疮性肾炎的作用及其机制:研究姜黄素通过抑制中性粒细胞迁移治疗狼疮肾炎的作用及其内在机制:方法:对两种狼疮小鼠模型(MRL/lpr小鼠和R848治疗小鼠)腹腔注射50 mg/kg姜黄素。H&E和Masson染色用于评估肾脏的组织病理学变化。免疫荧光用于评估免疫复合物的沉积。通过酶联免疫吸附试验(ELISA)和实时逆转录聚合酶反应(RT-PCR)检测炎症因子的表达,通过Western印迹检测蛋白质的表达:结果:我们发现姜黄素在改善MRL/lpr小鼠和R848诱导的狼疮小鼠的炎症状况方面具有显著的潜力。姜黄素能有效减缓炎症的发展,减少中性粒细胞的浸润及其释放的关键炎症因子,从而减轻肾脏组织的炎症。从机理上讲,姜黄素能显著抑制白细胞介素-8上调的p-PI3K、p-AKT和p-NF-κB的表达,从而减少中性粒细胞的迁移和炎症因子的释放:姜黄素通过抑制PI3K/AKT/NF-κB信号通路,明显抑制了肾脏中性粒细胞的募集和促炎因子的释放,为治疗LN提供了新的治疗靶点和药物策略。
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来源期刊
Lupus Science & Medicine
Lupus Science & Medicine RHEUMATOLOGY-
CiteScore
5.30
自引率
7.70%
发文量
88
审稿时长
15 weeks
期刊介绍: Lupus Science & Medicine is a global, peer reviewed, open access online journal that provides a central point for publication of basic, clinical, translational, and epidemiological studies of all aspects of lupus and related diseases. It is the first lupus-specific open access journal in the world and was developed in response to the need for a barrier-free forum for publication of groundbreaking studies in lupus. The journal publishes research on lupus from fields including, but not limited to: rheumatology, dermatology, nephrology, immunology, pediatrics, cardiology, hepatology, pulmonology, obstetrics and gynecology, and psychiatry.
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