Iridin Prevented Against Lipopolysaccharide-Induced Inflammatory Responses of Macrophages via Inactivation of PKM2-Mediated Glycolytic Pathways

doi:10.2147/JIR.S292244

	Iridin Prevented Against Lipopolysaccharide-Induced Inflammatory Responses of Macrophages via Inactivation of PKM2-Mediated Glycolytic Pathways
	Ying, Zhen-Hua 2; Li, Hui-Min 2; Yu, Wen-Ying 3; Yu, Chen-Huan 1,3,4
刊名	JOURNAL OF INFLAMMATION RESEARCH
	2021
卷号	14
关键词	isoflavone glycolysis Warburg effect PKM2 JAK/STATs NF-kappa B
DOI	10.2147/JIR.S292244
通讯作者	Yu, Chen-Huan(yuchenhuan2002@163.com)
英文摘要	Purpose: Abnormal glycolysis of immune cells contributed to the development of inflammatory response. Inhibition of this Warburg phenotype could be a promising strategy for preventing various inflammatory diseases. Iridin (IRD) is a natural isoflavone, and exerts anticancer, antioxidant, and anti-inflammatory effects. However, the underlying mechanism of IRD on acute inflammation remains unknown. In this study, the protective effects of IRD against lipopolysaccharide (LPS)-induced inflammation were investigated in murine macrophage RAW264.7 cells and in mice. Methods: The inhibition of IRD on NO production in culture medium was detected by Griess assay while the levels of TNF-alpha, IL-1 beta, and MCP-1 were detected by ELISA assay. The effects of IRD on OCR and ECAR levels in LPS-treated macrophages were monitored by using Seahorse Analyzer. The apoptosis rate as well as the release of ROS and NO of RAW264.7 cells were analyzed by flow cytometric assay. The protective effects of IRD were investigated on LPS-induced inflammation in mice. The expressions of PKM2 and its downstream (p-JAK1, p-STAT1, p-STAT3, p-p65, iNOS, and COX2) in cells and in lung tissues were detected by Western blotting analysis. Results: IRD treatment at the concentrations of 12.5-50 mu M significantly inhibited the productions of TNF-alpha, IL-1 beta, MCP-1, and ROS, and suppressed the levels of glucose uptake and lactic acid in LPS-treated RAW264.7 cells. Oral administration with IRD (20-80 mg/kg) inhibited LPS-induced acute lung injury as well as inflammatory cytokine production in mice. Moreover, IRD targeted pyruvate kinase isozyme type M2 (PKM2) and suppressed its downstream p-JAK1, p-STAT1, p-STAT3, p-p65, iNOS, and COX2, which could be abolished by PKM2 agonist DASA-58 and antioxidant N-acetyl-L-cysteine, but partly be reversed by NF-kappa B activator CUT129 and JAK1 activator RO8191. Conclusion: IRD alleviated LPS-induced inflammation through suppressing PKM2-mediated pathways, and could be a potential candidate for the prevention of inflammatory diseases.
资助项目	National Natural Science Foundation of China[81603368] ; National Natural Science Foundation of China[81673583] ; Zhejiang Provincial Science and Technology Project[2015C33164] ; Zhejiang Provincial Medicine and Technology Project[2020KY527] ; Zhejiang Innovation Discipline Project of Laboratory Animal Genetic Engineering[201604]
WOS关键词	BELAMCANDA-CHINENSIS ; CHEMICAL-CONSTITUENTS ; POLARIZATION ; METABOLISM ; CANCER ; PKM2
WOS研究方向	Immunology
语种	英语
出版者	DOVE MEDICAL PRESS LTD
WOS记录号	WOS:000619449000001
资助机构	National Natural Science Foundation of China ; Zhejiang Provincial Science and Technology Project ; Zhejiang Provincial Medicine and Technology Project ; Zhejiang Innovation Discipline Project of Laboratory Animal Genetic Engineering
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/120185]
专题	中国科学院合肥物质科学研究院
通讯作者	Yu, Chen-Huan
作者单位	1.Chinese Acad Sci, Inst Canc & Basic Med, Hangzhou 310018, Peoples R China 2.Zhejiang Prov Peoples Hosp, Hangzhou Med Coll, Hangzhou 310006, Peoples R China 3.Hangzhou Med Coll, Zhejiang Key Lab Expt Anim & Safety Evaluat, Hangzhou 310013, Peoples R China 4.Univ Chinese Acad Sci, Canc Hosp, Zhejiang Canc Hosp, Hangzhou 310022, Zhejiang, Peoples R China
推荐引用方式 GB/T 7714	Ying, Zhen-Hua,Li, Hui-Min,Yu, Wen-Ying,et al. Iridin Prevented Against Lipopolysaccharide-Induced Inflammatory Responses of Macrophages via Inactivation of PKM2-Mediated Glycolytic Pathways[J]. JOURNAL OF INFLAMMATION RESEARCH,2021,14.
APA	Ying, Zhen-Hua,Li, Hui-Min,Yu, Wen-Ying,&Yu, Chen-Huan.(2021).Iridin Prevented Against Lipopolysaccharide-Induced Inflammatory Responses of Macrophages via Inactivation of PKM2-Mediated Glycolytic Pathways.JOURNAL OF INFLAMMATION RESEARCH,14.
MLA	Ying, Zhen-Hua,et al."Iridin Prevented Against Lipopolysaccharide-Induced Inflammatory Responses of Macrophages via Inactivation of PKM2-Mediated Glycolytic Pathways".JOURNAL OF INFLAMMATION RESEARCH 14(2021).