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盐酸麻黄碱可保护小鼠免受诱导性腹膜炎的侵害。

Ephedrine hydrochloride protects mice from -induced peritonitis.

作者信息

He Weigang, Ma Jinzhu, Chen Yijian, Jiang Xinru, Wang Yuli, Shi Ting, Zhang Qingwen, Yang Yang, Jiang Xin, Yin Shulei, Zheng Aoxiang, Lu Jie, Zheng Yuejuan

机构信息

Department of Immunology and Microbiology, Shanghai University of Traditional Chinese MedicineShanghai 201203, China.

College of Life Science and Technology, Heilongjiang Bayi Agricultural UniversityDaqing 163319, China.

出版信息

Am J Transl Res. 2018 Mar 15;10(3):670-683. eCollection 2018.

Abstract

is a Gram-positive (G) bacterium that causes a wide range of diseases in humans and livestock. Therefore, the development of innovative and effective therapies is essential for the treatment of -induced severe infections. Ephedrine hydrochloride (EH) is a compound derived from ephedrine and is widely used for the management of cardiovascular diseases and hypotension. The results of our previous studies demonstrated that EH has anti-inflammatory activity in macrophages and protects against endotoxic shock. However, whether EH regulates the function of dendritic cells (DCs) and the immune response in -induced infection is unknown. In this study, the anti-inflammatory and regulatory activity of EH on DCs was evaluated. EH increased the production of anti-inflammatory cytokine IL-10 and decreased the production of proinflammatory cytokines TNF-α and IL-12 in DCs stimulated with peptidoglycan (PGN), the main cell wall component in G bacteria. The PI3K/Akt and p38 MAPK signaling pathways controlled EH-induced IL-10 expression and EH-inhibited TNF-α expression, respectively. The PGN-induced expression of co-stimulatory molecules CD40, CD80, CD86, and MHC class II molecule Iab was down-regulated in DCs by EH. Furthermore, EH protected the liver and kidney and increased the survival rate of mice with -induced peritonitis. In conclusion, EH helps to keep immune homeostasis and alleviate organ damage during -induced peritonitis. Therefore, EH may be a promising drug candidate in the treatment of -induced severe infections and other invasive G bacterial infections.

摘要

是一种革兰氏阳性(G)细菌,可导致人类和牲畜的多种疾病。因此,开发创新有效的治疗方法对于治疗由其引起的严重感染至关重要。盐酸麻黄碱(EH)是一种从麻黄碱衍生而来的化合物,广泛用于治疗心血管疾病和低血压。我们先前研究的结果表明,EH在巨噬细胞中具有抗炎活性,并能预防内毒素休克。然而,EH是否调节树突状细胞(DCs)的功能以及在其诱导的感染中的免疫反应尚不清楚。在本研究中,评估了EH对DCs的抗炎和调节活性。在由G细菌的主要细胞壁成分肽聚糖(PGN)刺激的DCs中,EH增加了抗炎细胞因子IL-10的产生,并降低了促炎细胞因子TNF-α和IL-12的产生。PI3K/Akt和p38 MAPK信号通路分别控制EH诱导的IL-10表达和EH抑制的TNF-α表达。EH下调了DCs中PGN诱导的共刺激分子CD40、CD80、CD86和MHC II类分子Iab的表达。此外,EH保护肝脏和肾脏,并提高了患有其诱导的腹膜炎小鼠的存活率。总之,EH有助于在其诱导的腹膜炎期间维持免疫稳态并减轻器官损伤。因此,EH可能是治疗其诱导的严重感染和其他侵袭性G细菌感染的有前途的候选药物。

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