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脂多糖诱导的中枢神经系统炎症通过激活小鼠肝脏中的IL-6/JAK2/STAT3途径上调肝铁调素表达。

Central Nervous System Inflammation Induced by Lipopolysaccharide Up-Regulates Hepatic Hepcidin Expression by Activating the IL-6/JAK2/STAT3 Pathway in Mice.

作者信息

Zhang Fali, Zhao Peng, Qian Zhongming, Zhong Mingkang

机构信息

Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, China.

Institute of Translational & Precision Medicine, Laboratory of Neuropharmacology, Nantong University, Nantong, China.

出版信息

Front Nutr. 2021 Apr 1;8:649640. doi: 10.3389/fnut.2021.649640. eCollection 2021.

Abstract

It is known that lipopolysaccharide (LPS) triggers inflammatory response after intracerebroventricular (ICV) injection and elevates the expression of hepcidin through the interleukin 6/janus kinase 2/transducer and activator of the transcription 3 (IL-6/JAK2/STAT3) signaling pathway in the brain. This study was conducted to determine whether LPS ICV injection can regulate peripheral hepatic hepcidin expression and iron metabolism. Here, we studied the hepcidin expression in the liver, as well as serum iron and transferrin saturation, after LPS ICV injection. We also demonstrated the role of the IL-6/JAK2/STAT3 pathway in hepcidin expression in the livers of IL-6 knockout (IL-6-/- mice) and IL-6+/+ mice. AG490 was used to verify the effect of the IL-6/JAK2/STAT3 pathway on hepatic hepcidin expression. Our present study demonstrated that LPS ICV injection up-regulated hepatic hepcidin expression. This finding provides further evidence for highlighting the importance of the central inflammation on hepatic hepcidin expression and peripheral iron metabolism.

摘要

已知脂多糖(LPS)在脑室内(ICV)注射后会引发炎症反应,并通过大脑中的白细胞介素6/ Janus激酶2/转录3信号转导子和激活子(IL-6/JAK2/STAT3)信号通路提高铁调素的表达。本研究旨在确定ICV注射LPS是否能调节外周肝脏铁调素的表达和铁代谢。在此,我们研究了ICV注射LPS后肝脏中铁调素的表达以及血清铁和转铁蛋白饱和度。我们还证实了IL-6/JAK2/STAT3通路在白细胞介素6基因敲除(IL-6-/-小鼠)和IL-6+/+小鼠肝脏铁调素表达中的作用。AG490用于验证IL-6/JAK2/STAT3通路对肝脏铁调素表达的影响。我们目前的研究表明,ICV注射LPS会上调肝脏铁调素的表达。这一发现为强调中枢炎症对肝脏铁调素表达和外周铁代谢的重要性提供了进一步的证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5de/8046903/9124bd5aa998/fnut-08-649640-g0001.jpg

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