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苦参碱通过抑制气道上皮细胞和哮喘小鼠中的NF-κB信号通路下调SOCS3表达来抑制气道炎症。

Matrine suppresses airway inflammation by downregulating SOCS3 expression via inhibition of NF-κB signaling in airway epithelial cells and asthmatic mice.

作者信息

Sun Daqing, Wang Jing, Yang Niandi, Ma Haixin

机构信息

Department of Respiration, Xi'an Children's Hospital, Xi'an 710003, PR China.

Department of Neonatology, Xi'an Children's Hospital, Xi'an 710003, PR China.

出版信息

Biochem Biophys Res Commun. 2016 Aug 12;477(1):83-90. doi: 10.1016/j.bbrc.2016.06.024. Epub 2016 Jun 7.

DOI:10.1016/j.bbrc.2016.06.024
PMID:27286706
Abstract

UNLABELLED

Matrine has been demonstrated to attenuate allergic airway inflammation. Elevated suppressor of cytokine signaling 3 (SOCS3) was correlated with the severity of asthma. The aim of this study was to investigate the effect of matrine on SOCS3 expression in airway inflammation. In this study, we found that matrine significantly inhibited OVA-induced AHR, inflammatory cell infiltration, goblet cell differentiation, and mucous production in a dose-dependent manner in mice. Matrine also abrogated the level of interleukin (IL)-4 and IL-13, but enhanced interferon (IFN)-γ expression, both in BALF and in lung homogenates. Furthermore, matrine impeded TNF-α-induced the expression of IL-6 and adhesion molecules in airway epithelial cells (BEAS-2B and MLE-12). Additionally, we found that matrine inhibited SOCS3 expression, both in asthmatic mice and TNF-α-stimulated epithelial cells via suppression of the NF-κB signaling pathway by using pcDNA3.1-SOCS3 plasmid, SOCS3 siRNA, or nuclear factor kappa-B (NF-κB) inhibitor PDTC.

CONCLUSIONS

Matrine suppresses airway inflammation by downregulating SOCS3 expression via inhibition of NF-κB signaling in airway epithelial cells and asthmatic mice.

摘要

未标记

已证明苦参碱可减轻过敏性气道炎症。细胞因子信号传导抑制因子3(SOCS3)水平升高与哮喘严重程度相关。本研究旨在探讨苦参碱对气道炎症中SOCS3表达的影响。在本研究中,我们发现苦参碱能以剂量依赖的方式显著抑制小鼠卵清蛋白(OVA)诱导的气道高反应性(AHR)、炎性细胞浸润、杯状细胞分化和黏液分泌。苦参碱还能降低支气管肺泡灌洗液(BALF)和肺匀浆中白细胞介素(IL)-4和IL-13的水平,但能增强干扰素(IFN)-γ的表达。此外,苦参碱可抑制肿瘤坏死因子-α(TNF-α)诱导的气道上皮细胞(BEAS-2B和MLE-12)中IL-6和黏附分子的表达。此外,我们发现通过使用pcDNA3.1-SOCS3质粒、SOCS3小干扰RNA(siRNA)或核因子κB(NF-κB)抑制剂吡咯烷二硫代氨基甲酸盐(PDTC),苦参碱可抑制哮喘小鼠和TNF-α刺激的上皮细胞中SOCS3的表达,其机制是通过抑制NF-κB信号通路实现的。

结论

苦参碱通过抑制气道上皮细胞和哮喘小鼠中的NF-κB信号通路,下调SOCS3表达,从而抑制气道炎症。

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