Milk Fat Globule-Epidermal Growth Factor-Factor 8 Reverses Lipopolysaccharide-Induced Microglial Oxidative Stress

Overview

Journal Oxid Med Cell Longev

Publisher Wiley

Specialties Cell Biology
Endocrinology

Date 2019 Apr 20

PMID 31001372

Citations 12

Authors

Jie Li

Xiaotian Xu

Xiaoying Cai

Yinlun Weng

Yiping Wang

Qingyu Shen

Xiaolei Shi

Affiliations

Soon will be listed here.

Abstract

Oxidative stress plays an important role in various neurological disorders. Milk fat globule-epidermal growth factor-factor 8 (MFG-E8) is a regulatory protein for microglia. However, its involvement in microglial oxidative stress has not been established. In this study, we observed microglial oxidative stress in response to lipopolysaccharide (LPS) both and . LPS induced significant elevation of TNF-, IL-6, MDA, and ROS and reduction of GSH and SOD in the mouse brains and primary microglia, which were reversed by MFG-E8 pretreatment. MFG-E8 induced the expression of Nrf-2 and HO-1 that was reduced by LPS incubation. Moreover, LPS-increased Keap-1 expression was reversed by MFG-E8. But the above tendencies were not seen when MFG-E8 was applied alone. The current study established the involvement of MFG-E8 in antioxidant effects during neuroinflammation. It may achieve the effects through the regulation of Keap-1/Nrf-2/HO-1 pathways.

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References

Villalba M, Martinez-Serrano A, Borner C, Blanco P, Satrustegui J . NMDA-induced increase in [Ca2+]i and 45Ca2+ uptake in acutely dissociated brain cells derived from adult rats. Brain Res. 1992; 570(1-2):347-53. DOI: 10.1016/0006-8993(92)90600-e. View

Akakura S, Singh S, Spataro M, Akakura R, Kim J, Albert M . The opsonin MFG-E8 is a ligand for the alphavbeta5 integrin and triggers DOCK180-dependent Rac1 activation for the phagocytosis of apoptotic cells. Exp Cell Res. 2003; 292(2):403-16. DOI: 10.1016/j.yexcr.2003.09.011. View

Nimmerjahn A, Kirchhoff F, Helmchen F . Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science. 2005; 308(5726):1314-8. DOI: 10.1126/science.1110647. View

Raymond A, Ensslin M, Shur B . SED1/MFG-E8: a bi-motif protein that orchestrates diverse cellular interactions. J Cell Biochem. 2009; 106(6):957-66. PMC: 2742659. DOI: 10.1002/jcb.22076. View

Tseng Y, Hsu Y, Shih Y, Lo Y . Paeonol attenuates microglia-mediated inflammation and oxidative stress-induced neurotoxicity in rat primary microglia and cortical neurons. Shock. 2011; 37(3):312-8. DOI: 10.1097/SHK.0b013e31823fe939. View

Fricker M, Neher J, Zhao J, Thery C, Tolkovsky A, Brown G . MFG-E8 mediates primary phagocytosis of viable neurons during neuroinflammation. J Neurosci. 2012; 32(8):2657-66. PMC: 3312099. DOI: 10.1523/JNEUROSCI.4837-11.2012. View

Wohleb E, Fenn A, Pacenta A, Powell N, Sheridan J, Godbout J . Peripheral innate immune challenge exaggerated microglia activation, increased the number of inflammatory CNS macrophages, and prolonged social withdrawal in socially defeated mice. Psychoneuroendocrinology. 2012; 37(9):1491-505. PMC: 3368999. DOI: 10.1016/j.psyneuen.2012.02.003. View

Neniskyte U, Brown G . Lactadherin/MFG-E8 is essential for microglia-mediated neuronal loss and phagoptosis induced by amyloid β. J Neurochem. 2013; 126(3):312-7. DOI: 10.1111/jnc.12288. View

Benarroch E . Microglia: Multiple roles in surveillance, circuit shaping, and response to injury. Neurology. 2013; 81(12):1079-88. DOI: 10.1212/WNL.0b013e3182a4a577. View

10.

Bogie J, Stinissen P, Hendriks J . Macrophage subsets and microglia in multiple sclerosis. Acta Neuropathol. 2014; 128(2):191-213. DOI: 10.1007/s00401-014-1310-2. View

11.

Park J, Min J, Kim B, Chae U, Yun J, Choi M . Mitochondrial ROS govern the LPS-induced pro-inflammatory response in microglia cells by regulating MAPK and NF-κB pathways. Neurosci Lett. 2014; 584:191-6. DOI: 10.1016/j.neulet.2014.10.016. View

12.

Shi X, Zheng Z, Li J, Xiao Z, Qi W, Zhang A . Curcumin inhibits Aβ-induced microglial inflammatory responses in vitro: Involvement of ERK1/2 and p38 signaling pathways. Neurosci Lett. 2015; 594:105-10. DOI: 10.1016/j.neulet.2015.03.045. View

13.

Cheyuo C, Aziz M, Yang W, Jacob A, Zhou M, Wang P . Milk fat globule-EGF factor VIII attenuates CNS injury by promoting neural stem cell proliferation and migration after cerebral ischemia. PLoS One. 2015; 10(4):e0122833. PMC: 4394995. DOI: 10.1371/journal.pone.0122833. View

14.

Kato T, Hyodo F, Yamato M, Utsumi H, Kanba S . [Redox and microglia in the pathophysiology of schizophrenia]. Yakugaku Zasshi. 2015; 135(5):739-43. DOI: 10.1248/yakushi.14-00235-4. View

15.

Norden D, Trojanowski P, Villanueva E, Navarro E, Godbout J . Sequential activation of microglia and astrocyte cytokine expression precedes increased Iba-1 or GFAP immunoreactivity following systemic immune challenge. Glia. 2015; 64(2):300-16. PMC: 4707977. DOI: 10.1002/glia.22930. View

16.

Di W, Shi X, Lv H, Liu J, Zhang H, Li Z . Activation of the nuclear factor E2-related factor 2/anitioxidant response element alleviates the nitroglycerin-induced hyperalgesia in rats. J Headache Pain. 2016; 17(1):99. PMC: 5078120. DOI: 10.1186/s10194-016-0694-x. View

17.

Shi X, Cai X, Di W, Li J, Xu X, Zhang A . MFG-E8 Selectively Inhibited Aβ-Induced Microglial M1 Polarization via NF-κB and PI3K-Akt Pathways. Mol Neurobiol. 2016; 54(10):7777-7788. DOI: 10.1007/s12035-016-0255-y. View

18.

Hendricks L, Aziz M, Yang W, Nicastro J, Coppa G, Symons M . Milk fat globule-epidermal growth factor-factor VIII-derived peptide MSP68 is a cytoskeletal immunomodulator of neutrophils that inhibits Rac1. J Surg Res. 2016; 208:10-19. PMC: 5180211. DOI: 10.1016/j.jss.2016.08.098. View

19.

Luckoff A, Scholz R, Sennlaub F, Xu H, Langmann T . Comprehensive analysis of mouse retinal mononuclear phagocytes. Nat Protoc. 2017; 12(6):1136-1150. DOI: 10.1038/nprot.2017.032. View

20.

Huang X, Liao W, Huang Y, Jiang M, Chen J, Wang M . Neuroprotective effect of dual specificity phosphatase 6 against glutamate-induced cytotoxicity in mouse hippocampal neurons. Biomed Pharmacother. 2017; 91:385-392. DOI: 10.1016/j.biopha.2017.04.096. View