5-HMF Attenuates Inflammation and Demyelination in Experimental Autoimmune Encephalomyelitis Mice by Inhibiting the MIF-CD74 Interaction

Overview

Journal Acta Biochim Biophys Sin (Shanghai)

Specialties Biochemistry
Biophysics

Date 2023 Jul 11

PMID 37431183

Authors

Dongsheng Guan

Yingxia Li

Yinglin Cui

Huanghong Zhao

Ning Dong

Kun Wang

Deqi Ren

Tiantian Song

Xiaojing Wang

Shijie Jin

Yinghe Gao

Mengmeng Wang

Affiliations

Soon will be listed here.

Abstract

The neuroprotective role of 5-hydroxymethyl-2-furfural (5-HMF) has been demonstrated in a variety of neurological diseases. The aim of this study is to investigate the effect of 5-HMF on multiple sclerosis (MS). IFN-γ-stimulated murine microglia (BV2 cells) are considered a cell model of MS. With 5-HMF treatment, microglial M1/2 polarization and cytokine levels are detected. The interaction of 5-HMF with migration inhibitory factor (MIF) is predicted using online databases. The experimental autoimmune encephalomyelitis (EAE) mouse model is established, followed by a 5-HMF injection. The results show that 5-HMF facilitates IFN-γ-stimulated microglial M2 polarization and attenuates the inflammatory response. According to the network pharmacology and molecular docking results, 5-HMF has a binding site for MIF. Further results show that blocking MIF activity or silencing enhances microglial M2 polarization, reduces inflammatory activity, and prevents ERK1/2 phosphorylation. 5-HMF inhibits the MIF-CD74 interaction by binding to MIF, thereby inhibiting microglial M1 polarization and enhancing the anti-inflammatory response. 5-HMF ameliorates EAE, inflammation, and demyelination . In conclusion, our research indicates that 5-HMF promotes microglial M2 polarization by inhibiting the MIF-CD74 interaction, thereby attenuating inflammation and demyelination in EAE mice.

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References

Cox G, Kithcart A, Pitt D, Guan Z, Alexander J, Williams J . Macrophage migration inhibitory factor potentiates autoimmune-mediated neuroinflammation. J Immunol. 2013; 191(3):1043-54. DOI: 10.4049/jimmunol.1200485. View

Lassmann H, van Horssen J, Mahad D . Progressive multiple sclerosis: pathology and pathogenesis. Nat Rev Neurol. 2012; 8(11):647-56. DOI: 10.1038/nrneurol.2012.168. View

Sumaiya K, Langford D, Natarajaseenivasan K, Shanmughapriya S . Macrophage migration inhibitory factor (MIF): A multifaceted cytokine regulated by genetic and physiological strategies. Pharmacol Ther. 2021; 233:108024. DOI: 10.1016/j.pharmthera.2021.108024. View

Jin X, Liu M, Zhang D, Zhong X, Du K, Qian P . Natural products as a potential modulator of microglial polarization in neurodegenerative diseases. Pharmacol Res. 2019; 145:104253. DOI: 10.1016/j.phrs.2019.104253. View

Zhang Y, Xu L, Zhang Y, Pan J, Wang P, Tian S . Discovery of novel MIF inhibitors that attenuate microglial inflammatory activation by structures-based virtual screening and in vitro bioassays. Acta Pharmacol Sin. 2021; 43(6):1508-1520. PMC: 9160002. DOI: 10.1038/s41401-021-00753-x. View

Orihuela R, McPherson C, Harry G . Microglial M1/M2 polarization and metabolic states. Br J Pharmacol. 2015; 173(4):649-65. PMC: 4742299. DOI: 10.1111/bph.13139. View

Filippi M, Bar-Or A, Piehl F, Preziosa P, Solari A, Vukusic S . Multiple sclerosis. Nat Rev Dis Primers. 2018; 4(1):43. DOI: 10.1038/s41572-018-0041-4. View

Wang M, Pan W, Xu Y, Zhang J, Wan J, Jiang H . Microglia-Mediated Neuroinflammation: A Potential Target for the Treatment of Cardiovascular Diseases. J Inflamm Res. 2022; 15:3083-3094. PMC: 9148574. DOI: 10.2147/JIR.S350109. View

Zhu J, Qian W, Wang Y, Gao R, Wang J, Xiao H . Involvement of mitogen-activated protein kinase and NF-κB signaling pathways in perfluorooctane sulfonic acid-induced inflammatory reaction in BV2 microglial cells. J Appl Toxicol. 2015; 35(12):1539-49. DOI: 10.1002/jat.3119. View

10.

Godfrey V, Chen L, Griffin R, Lebetkin E, Burka L . Distribution and metabolism of (5-hydroxymethyl)furfural in male F344 rats and B6C3F1 mice after oral administration. J Toxicol Environ Health A. 1999; 57(3):199-210. DOI: 10.1080/009841099157764. View

11.

Miron V, Franklin R . Macrophages and CNS remyelination. J Neurochem. 2014; 130(2):165-71. DOI: 10.1111/jnc.12705. View

12.

DAmato-Brito C, Cipriano D, Colin D, Germain S, Seimbille Y, Robert J . Role of MIF/CD74 signaling pathway in the development of pleural mesothelioma. Oncotarget. 2016; 7(10):11512-25. PMC: 4905490. DOI: 10.18632/oncotarget.7314. View

13.

Geng Y, Zhu S, Cheng P, Lu Z, Xu H, Shi J . Bioassay-guided fractionation of ethyl acetate extract from Armillaria mellea attenuates inflammatory response in lipopolysaccharide (LPS) stimulated BV-2 microglia. Phytomedicine. 2017; 26:55-61. DOI: 10.1016/j.phymed.2017.01.005. View

14.

Li Y, Zhou D, Ren Y, Zhang Z, Guo X, Ma M . Mir223 restrains autophagy and promotes CNS inflammation by targeting ATG16L1. Autophagy. 2018; 15(3):478-492. PMC: 6351131. DOI: 10.1080/15548627.2018.1522467. View

15.

An J, Zhang W, Zhang J, Lian L, Shen Y, Ding W . Vitamin D improves the content of TGF-β and IGF-1 in intervertebral disc of diabetic rats. Exp Biol Med (Maywood). 2017; 242(12):1254-1261. PMC: 5476342. DOI: 10.1177/1535370217707744. View

16.

He Y, Li M, Wu L, Zhao T, Di Y, Huang X . Enhanced hypoxia-inducible factor (HIF)-1α stability induced by 5-hydroxymethyl-2-furfural (5-HMF) contributes to protection against hypoxia. Mol Med. 2014; 20:590-600. PMC: 4365066. DOI: 10.2119/molmed.2014.00007. View

17.

Mazzon C, Zanotti L, Wang L, Del Prete A, Fontana E, Salvi V . CCRL2 regulates M1/M2 polarization during EAE recovery phase. J Leukoc Biol. 2016; 99(6):1027-33. DOI: 10.1189/jlb.3MA0915-444RR. View

18.

Miao Q, Zhang X, Han Q, Ren S, Sui R, Yu J . The therapeutic potential of bilobalide on experimental autoimmune encephalomyelitis (EAE) mice. Metab Brain Dis. 2020; 35(5):793-807. DOI: 10.1007/s11011-020-00555-w. View

19.

Chu F, Shi M, Zheng C, Shen D, Zhu J, Zheng X . The roles of macrophages and microglia in multiple sclerosis and experimental autoimmune encephalomyelitis. J Neuroimmunol. 2018; 318:1-7. DOI: 10.1016/j.jneuroim.2018.02.015. View

20.

Riedemann N, Guo R, Gao H, Sun L, Hoesel M, Hollmann T . Regulatory role of C5a on macrophage migration inhibitory factor release from neutrophils. J Immunol. 2004; 173(2):1355-9. DOI: 10.4049/jimmunol.173.2.1355. View