PMID- 35428692 OWN - NLM STAT- MEDLINE DCOM- 20220519 LR - 20220530 IS - 1550-6606 (Electronic) IS - 0022-1767 (Linking) VI - 208 IP - 10 DP - 2022 May 15 TI - Berberine Modulates Macrophage Activation by Inducing Glycolysis. PG - 2309-2318 LID - 10.4049/jimmunol.2100716 [doi] AB - Classical activation of macrophage and monocyte differentiation induced by beta-glucan is accompanied with metabolic change in glucose. However, the role of the metabolic rewiring in monocyte/macrophage activation remains elusive. In this study, we show that berberine induces aerobic glycolysis by blocking the tricarboxylic acid cycle and modulates cytokine responses in bone marrow-derived macrophages (BMDMs) from mice and human PBMC. 13-Methyberberine had activities on glucose metabolism and BMDM activation similar to those of berberine, whereas other tested derivatives lost both activities. Glucose transporter (GLUT)1 expression and total cellular hexokinase activity increased gradually in BMDMs in the presence of berberine. In the contrast, LPS upregulated GLUT1 and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) levels in 6 h. Extracellular glucose levels and replacing glucose with galactose in culture medium affected the cytokine secretion of BMDMs. Berberine alleviated enteritis of Salmonella typhimurium infection and protected mice against endotoxic shock. In mice i.p. injected with LPS, the increase of serum TNF-alpha and the drop of blood glucose were attenuated by berberine treatment. These data together demonstrated that macrophage activation was closely related with glucose metabolism. CI - Copyright (c) 2022 by The American Association of Immunologists, Inc. FAU - Li, Min AU - Li M AD - Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China; and. FAU - Zhang, Haifeng AU - Zhang H AD - Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China; and. FAU - Zhang, Yameng AU - Zhang Y AD - Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China; and. FAU - Fan, Jinting AU - Fan J AD - Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China; and. FAU - Zhu, Jinhao AU - Zhu J AUID- ORCID: 0000-0002-5730-3155 AD - Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China; and. FAU - Gu, Xinyue AU - Gu X AD - Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China; and. FAU - Li, Zhonghui AU - Li Z AUID- ORCID: 0000-0001-8762-7612 AD - Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China; and. FAU - Zhang, Chengyang AU - Zhang C AD - Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China; and. FAU - Liu, Zhen AU - Liu Z AD - College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou, China. FAU - Li, Yuebai AU - Li Y AD - Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China; and. FAU - Zang, Mingxi AU - Zang M AD - Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China; and. FAU - Jin, Ge AU - Jin G AD - Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China; and. FAU - Li, Guoping AU - Li G AD - College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou, China. FAU - Mi, Yang AU - Mi Y AUID- ORCID: 0000-0002-2585-9917 AD - Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China; and miyang@zzu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220415 PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Lipopolysaccharides) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0I8Y3P32UF (Berberine) RN - EC 2.7.1.105 (Phosphofructokinase-2) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - *Berberine/pharmacology MH - Glucose MH - Glycolysis MH - Leukocytes, Mononuclear/metabolism MH - Lipopolysaccharides/metabolism MH - *Macrophage Activation MH - Mice MH - Phosphofructokinase-2/metabolism MH - Tumor Necrosis Factor-alpha/metabolism EDAT- 2022/04/17 06:00 MHDA- 2022/05/20 06:00 CRDT- 2022/04/16 05:20 PHST- 2021/07/19 00:00 [received] PHST- 2022/02/28 00:00 [accepted] PHST- 2022/04/17 06:00 [pubmed] PHST- 2022/05/20 06:00 [medline] PHST- 2022/04/16 05:20 [entrez] AID - jimmunol.2100716 [pii] AID - 10.4049/jimmunol.2100716 [doi] PST - ppublish SO - J Immunol. 2022 May 15;208(10):2309-2318. doi: 10.4049/jimmunol.2100716. Epub 2022 Apr 15.