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炎症小体:肝脏疾病的双刃剑。

Inflammasome: A Double-Edged Sword in Liver Diseases.

机构信息

Department of Microbiological and Biochemical Pharmacy & The Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai, China.

出版信息

Front Immunol. 2018 Sep 25;9:2201. doi: 10.3389/fimmu.2018.02201. eCollection 2018.

Abstract

Inflammasomes have emerged as critical innate sensors of host immune that defense against pathogen infection, metabolism syndrome, cellular stress and cancer metastasis in the liver. The assembly of inflammasome activates caspase-1, which promotes the maturation of interleukin-1β (IL-1β) and interleukin-18 (IL-18), and initiates pyroptotic cell death (pyroptosis). IL-18 exerts pleiotropic effects on hepatic NK cells, priming FasL-mediated cytotoxicity, and interferon-γ (IFN-γ)-dependent responses to prevent the development of liver diseases. However, considerable attention has been attracted to the pathogenic role of inflammasomes in various acute and chronic liver diseases, including viral hepatitis, nanoparticle-induced liver injury, alcoholic and non-alcoholic steatohepatitis. In this review, we summarize the latest advances on the physiological and pathological roles of inflammasomes for further development of inflammasome-based therapeutic strategies for human liver diseases.

摘要

炎症小体已成为宿主免疫防御的关键先天传感器,可抵御病原体感染、代谢综合征、细胞应激和肝转移。炎症小体的组装激活半胱氨酸蛋白酶-1(caspase-1),促进白细胞介素-1β(IL-1β)和白细胞介素-18(IL-18)的成熟,并启动细胞焦亡(pyroptosis)。IL-18 对肝 NK 细胞具有多效作用,增强 FasL 介导的细胞毒性和干扰素-γ(IFN-γ)依赖性反应,以防止肝脏疾病的发生。然而,炎症小体在各种急慢性肝病(包括病毒性肝炎、纳米颗粒诱导的肝损伤、酒精性和非酒精性脂肪性肝炎)中的致病作用引起了相当大的关注。在这篇综述中,我们总结了炎症小体在生理和病理方面的最新进展,以期为人类肝脏疾病的炎症小体为基础的治疗策略的进一步发展提供参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42e9/6167446/6d1458b76daa/fimmu-09-02201-g0001.jpg

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