研究动态
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青蒿素在巨噬细胞中减轻人细小病毒B19 NS1诱导的NLRP3炎性小体的活化。

Celastrol attenuates human parvovirus B19 NS1‑induced NLRP3 inflammasome activation in macrophages.

发表日期:2023 Oct
作者: Chang-Lun Huang, Der-Yuan Chen, Chih-Chen Tzang, Jhen-Wei Lin, Bor-Show Tzang, Tsai-Ching Hsu
来源: CYTOKINE & GROWTH FACTOR REVIEWS

摘要:

人绒毛膜炎病毒B19 (B19V) 与多种炎症性疾病密切相关,例如风湿性关节炎 (RA)、炎症性肠病和系统性红斑狼疮。B19V的非结构蛋白1 (NS1) 在B19V感染的病理过程中被证实在炎性细胞因子的调控方面起到重要作用。吴茱萸素 (Celastrol) 是一种从雷公藤中分离出的苯醌甲素,已显示出在治疗银屑病和RA等炎症性疾病方面具有显著潜力。然而,关于吴茱萸素对B19V NS1诱导的炎症的影响,目前了解甚少。因此,我们进行了细胞活力实验、细胞迁移实验、吞噬作用分析、酶切分析、ELISA和免疫印迹实验,以验证吴茱萸素对巨噬细胞的影响。本研究报道了吴茱萸素对从人类急性单核白血病细胞系U937和THP-1中分化得到的巨噬免疫细胞中的B19V NS1诱导的炎症反应的减轻作用。尽管在U937和THP-1巨噬细胞中,吴茱萸素对迁移的影响没有显著下降,但在存在吴茱萸素条件下,B19V NS1激活的U937和THP-1巨噬细胞的存活率、迁移能力和吞噬作用均显著降低。此外,吴茱萸素显著降低了B19V NS1激活的U937和THP-1细胞中MMP-9的活性以及炎性细胞因子IL-6、TNF-α和IL-1β的水平。值得注意的是,在存在吴茱萸素的条件下,B19V NS1激活的U937和THP-1细胞中NLR家族熟果蛋白结构域3、跟凋亡相关的斑点样蛋白、半胱氨酸天冬酰基酶-1和IL-18蛋白的水平均显著降低,显示出炎症小体通路的参与。据我们所知,本研究是首次报道了吴茱萸素对B19V NS1诱导的巨噬细胞炎症反应的减轻作用,这表明吴茱萸素在B19V NS1相关炎症性疾病中具有治疗作用。
Human parvovirus B19 (B19V) has been strongly associated with a variety of inflammatory disorders, such as rheumatoid arthritis (RA), inflammatory bowel disease and systemic lupus erythematosus. Non‑structural protein 1 (NS1) of B19V has been demonstrated to play essential roles in the pathological processes of B19V infection due to its regulatory properties on inflammatory cytokines. Celastrol, a quinone methide isolated from Tripterygium wilfordii, has displayed substantial potential in treating inflammatory diseases, such as psoriasis and RA. However, little is known about the effects of celastrol on B19V NS1‑induced inflammation. Therefore, cell viability assay, migration assay, phagocytosis analysis, zymography assay, ELISA and immunoblotting were conducted to verify the influences of celastrol on macrophages. The present study reported the attenuating effects of celastrol on B19V NS1‑induced inflammatory responses in macrophages derived from human acute monocytic leukemia cell lines, U937 and THP‑1. Although the migration was not significantly decreased by celastrol in both U937 and THP‑1 macrophages, significantly decreased viability, migration and phagocytosis were detected in both B19V NS1‑activated U937 and THP‑1 macrophages in the presence of celastrol. Additionally, celastrol significantly decreased MMP‑9 activity and the levels of inflammatory cytokines, including IL‑6, TNF‑α and IL‑1β, in B19V NS1‑activated U937 and THP‑1 cells. Notably, significantly decreased levels of NLR family pyrin domain‑containing 3, apoptosis‑associated speck‑like, caspase‑1 and IL‑18 proteins were observed in both B19V NS1‑activated U937 and THP‑1 cells in the presence of celastrol, indicating the involvement of the inflammasome pathway. To the best of our knowledge, the present study is the first to report on the attenuating effects of celastrol on B19V NS1‑induced inflammatory responses in macrophages, suggesting a therapeutic role for celastrol in B19V NS1‑related inflammatory diseases.