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

Yiping Wang,Yinlun Weng,Qingyu Shen,Xiaoying Cai,Jie Li,Xiaolei Shi,Xiaotian Xu

doi:10.1155/2019/2601394

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 in vitro and in vivo. LPS induced significant elevation of TNF-α, 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.

Highlights

Neuroinflammation plays an important role in the development of a set of neurological disorders, for example, cerebral infarction, Alzheimer’s Disease (AD), and multiple sclerosis [1,2,3,4]
We found the consistent changes in each group in vitro (Figure 2)
It showed that cells in controls occupied more grids than cells treated with LPS, and the tendency by LPS was significantly reversed by Milk fat globule-epidermal growth factor-factor 8 (MFG-E8) pretreatment

Summary

Introduction

Neuroinflammation plays an important role in the development of a set of neurological disorders, for example, cerebral infarction, Alzheimer’s Disease (AD), and multiple sclerosis [1,2,3,4]. Microglia account for 5% of the total cells in the brain, and they are key cells in balancing neuroinflammation. Once activated, they would produce a set of factors, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and reactive oxygen species (ROS) [5,6,7]. It is believed that effective modulation of microglial oxidative stress can be a therapeutic option for neurological disorders

Methods

Results

Conclusion