Low-dose lipopolysaccharide as an immune regulator for homeostasis maintenance in the central nervous system through transformation to neuroprotective microglia  

作　　者：Haruka Mizobuchi Gen-Ichiro Soma 

机构地区：[1]Control of Innate Immunity,Technology Research Association,Kagawa,Japan [2]Macrophi Inc.,Kagawa,Japan [3]Research Institute for Healthy Living,Niigata University of Pharmacy and Applied Life Sciences,Niigata,Japan

出　　处：《Neural Regeneration Research》2021年第10期1928-1934,共7页中国神经再生研究（英文版）

基　　金：This work was funded by Control of Innate Immunity Technology Research Association,a grant of Cross-ministerial Strategic Innovation Promotion Program,SIP-No.14533073(to GIS);from the Council for Science from Technology and Innovation(CSTI)in Cabinet Office of Japanese Government and the National Agriculture and Food Research Organization(NARO).

摘　　要：Microglia,which are tissue-resident macrophages in the brain,play a central role in the brain innate immunity and contribute to the maintenance of brain homeostasis.Lipopolysaccharide is a component of the outer membrane of gram-negative bacteria,and activates immune cells including microglia via Toll-like receptor 4 signaling.Lipopolysaccharide is generally known as an endotoxin,as administration of highdose lipopolysaccharide induces potent systemic inflammation.Also,it has long been recognized that lipopolysaccharide exacerbates neuroinflammation.In contrast,our study revealed that oral administration of lipopolysaccharide ameliorates Alzheimer’s disease pathology and suggested that neuroprotective microglia are involved in this phenomenon.Additionally,other recent studies have accumulated evidence demonstrating that controlled immune training with low-dose lipopolysaccharide prevents neuronal damage by transforming the microglia into a neuroprotective phenotype.Therefore,lipopolysaccharide may not a mere inflammatory inducer,but an immunomodulator that can lead to neuroprotective effects in the brain.In this review,we summarized current studies regarding neuroprotective microglia transformed by immune training with lipopolysaccharide.We state that microglia transformed by lipopolysaccharide preconditioning cannot simply be characterized by their general suppression of proinflammatory mediators and general promotion of anti-inflammatory mediators,but instead must be described by their complex profile comprising various molecules related to inflammatory regulation,phagocytosis,neuroprotection,anti-apoptosis,and antioxidation.In addition,microglial transformation seems to depend on the dose of lipopolysaccharide used during immune training.Immune training of neuroprotective microglia using lowdose lipopolysaccharide,especially through oral lipopolysaccharide administration,may represent an innovative prevention or treatment for neurological diseases;however more vigorous studies are still required to properly

关 键 词：cognitive impairment ENDOTOXIN LIPOPOLYSACCHARIDE LOW-DOSE MICROGLIA neuroprotection oral administration preconditioning tolerance trained innate immunity 

分 类 号：R965[医药卫生—药理学]