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熊果酸通过阻断 HMC-1 细胞内钙/半胱氨酸蛋白酶-1/NF-κB 信号级联反应下调胸腺基质淋巴细胞生成素。

Ursolic acid downregulates thymic stromal lymphopoietin through the blockade of intracellular calcium/caspase‑1/NF‑κB signaling cascade in HMC‑1 cells.

机构信息

Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.

Department of Food Science and Technology and Research Institute for Basic Science, Hoseo University, Asan, Chungnam 31499, Republic of Korea.

出版信息

Int J Mol Med. 2019 May;43(5):2252-2258. doi: 10.3892/ijmm.2019.4144. Epub 2019 Mar 22.

DOI:10.3892/ijmm.2019.4144
PMID:30976816
Abstract

Thymic stromal lymphopoietin (TSLP) plays an important role in allergic disorders, including atopic dermatitis and asthma. Ursolic acid (UA) has various pharmacological properties, such as antioxidant, anti‑inflammatory and anticancer. However, the effect of UA on TSLP regulation has not been fully elucidated. The aim of the present study was to analyze how UA regulates the production of TSLP in the human mast cell line HMC‑1. Enzyme‑linked immunosorbent assay, quantitative polymerase chain reaction analysis, western blotting, caspase‑1 assay and fluorescent measurements of intracellular calcium levels were conducted to analyze the regulatory effects of UA. The results revealed that UA inhibited TSLP production and mRNA expression. In addition, UA reduced the activation of nuclear factor‑κB and degradation of IκBα. Caspase‑1 activity was increased by exposure to phorbol myristate acetate plus calcium ionophore, whereas it was reduced by UA. Finally, UA treatment prevented an increase in intracellular calcium levels. These results indicated that UA may be a useful agent for the treatment and/or prevention of atopic and inflammatory diseases, and its effects are likely mediated by TSLP downregulation.

摘要

胸腺基质淋巴细胞生成素(TSLP)在过敏疾病中发挥着重要作用,包括特应性皮炎和哮喘。熊果酸(UA)具有多种药理作用,如抗氧化、抗炎和抗癌。然而,UA 对 TSLP 调节的影响尚未完全阐明。本研究旨在分析 UA 如何调节人肥大细胞系 HMC-1 中 TSLP 的产生。通过酶联免疫吸附试验、定量聚合酶链反应分析、western blot、半胱天冬酶-1 测定和细胞内钙离子水平的荧光测量来分析 UA 的调节作用。结果表明,UA 抑制 TSLP 的产生和 mRNA 表达。此外,UA 减少了核因子-κB 的激活和 IκBα 的降解。佛波醇肉豆蔻酸酯加钙离子载体刺激后,半胱天冬酶-1 活性增加,而 UA 则降低了半胱天冬酶-1 活性。最后,UA 处理可防止细胞内钙离子水平的升高。这些结果表明,UA 可能是治疗和/或预防特应性和炎症性疾病的有用药物,其作用可能通过 TSLP 的下调来介导。

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