Isocorydine Ameliorates IL-6 Expression in Bone Marrow-Derived Macrophages and Acute Lung Injury Induced by Lipopolysaccharide

Author:

Tu Yifan12,Li Xiaodong2,Fu Yuanzheng2,Chen Yunyun2,Fang Hui2,Li Yuan2,Gu Ying12,Zhang Jiawei1

Affiliation:

1. Key Laboratory of Cancer Prevention and Intervention of China National Ministry of Education, Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou 310009, China

2. Institute of Genetics, Department of Human Genetics, Zhejiang University School of Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China

Abstract

Isocorydine (ICD) is a type of isoquinoline alkaloid originating from Corydalis edulis, which has been used to relieve spasm, dilate blood vessels, and treat malaria as well as hypoxia in clinic. However, its effect on inflammation and underlying mechanisms remains unclear. The aim of our study was to determine the potential effects and mechanisms of ICD on pro-inflammatory interleukin-6 (IL-6) expression in bone marrow-derived macrophages (BMDMs) and acute lung injury mouse model. A mouse model of acute lung injury was established by intraperitoneal injection of LPS and treated with different doses of ICD. The body weight and food intake of mice were monitored to determine the toxicity of ICD. The tissue samples of lung, spleen and blood were taken to assess the pathological symptoms of acute lung injury and the expression levels of IL-6. Further, BMDMs isolated from C57BL/6 mice were cultured in vitro and treated with granulocyte-macrophage colony-stimulating factor (GM-CSF), LPS and different doses of ICD. CCK-8 assay and flow cytometry were performed to assess the viability of BMDMs. The expression of IL-6 was detected by RT-PCR and ELISA. RNA-seq was carried out to detect the differential expression genes of ICD-treated BMDMs. Western blotting was used to detect the change in MAPK and NF-κB signaling pathways. Our findings show that ICD ameliorates IL-6 expression and attenuates phosphorylation of p65 and JNK in BMDMs, and can protect mice from acute lung injury.

Funder

National Natural Science Foundation of China

Medical Health Science and Technology Project of Zhejiang Provincial Health Commission

the Zhejiang Innovation Team

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

Reference40 articles.

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