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Isoliquiritigenin suppresses microglial activation and neuroinflammation in primary microglia

中国药理学与毒理学杂志 2016年第10期30卷 1024-1024页

作者： FU Yan YANG Pin ZHAO Yang XU Ying Department of Physiology Shanghai University of Traditional Chinese Medicine

OBJECTIVE microglial activation contributes to neuroinflammation and neuronal damages in neurodegenerative disorders including Alzheimer and Parkinson *** has been suggested that neurodegenerative disorders may be improved if neuroinflammation can be ***(ISL)isolated from Glycyrrhiza glabra possess potent anti-inflammatory capability,we thus investigate the inhibitory effects of ISL on LPS-induced microglial activation and neuroinflammation and the roles of neuroprotection on neurodegenerative ***,we would explore the mechanism of itsassociated inflammatory signaling *** By cultivating,isolating and purifying,we got the primary microglia of the *** form of those cells was observed under an optical microscope,the purity was identified by the CD11b immunefluorescence ***,the effects of ISL on microglial viability were explored by the MTT *** microglial cells were pretreated by ISL(5μmol·L-1)and then stimulated by LPS(100 ng·mL-1),the production of NO was detected by Griess reagent,the change of microglial morphology was observed by immunefluorescence *** production of IL-1βand TNF-αin culture medium were tested by ELISA,and the m RNA expression of pro-inflammatory factors,including IL-1β,TNF-α,i NOS and COX-2 was detected by real time *** protein expression of i NOS and COX-2was detected by Western ***(1)After purifying,microglial showed the typical morphological *** cell body was small,protruding outstretched in the branch rod,*** LPS stimulation,the shape was changed to amoeba-like,and the protrusions retracted,cell *** the CD11b immunefluorescence staining,the purity of the microglial was over 98%,and showed powerful phagocytic activity.(2)The results show that ISL(0.16-20μmol·L-1)concentration has no effect on primary microglia′s *** at the concentration of 5μmol·L-1ISL has the significantly inhibitory effect on NO

关键词： isoliquiritigenin primary microglia inflammatory factors neuroinflammation

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A JNK signaling pathway is involved in LPS-induced indoleamine 2,3-dioxygenase expression in an interferon-γ-independent manner in primary murine microglia

A JNK signaling pathway is involved in LPS-induced indoleami...

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中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： Marcus A.Lawson Robert Dantzer Keith W.Kelley Integrative Immunology and Behavior Program Department of Animal Sciences College of ACESUniversity of Illinois at Urbana-ChampaignUSA

＜正＞Chronic inflammation is often associated with clinical *** studies have focused on potential mechanisms that might link inflammation-induced depression to tryptophan metabolism,particularly in the brain,where a reduction in the bioavailability of tryptophan could affect serotoninergic neurotransmission and play a synergistic role in the induction of depressive symptoms.A pivotal protein that has recently been shown to be required for development of inflammation-induced depressive-like behavior in mice is indoleamine 2,3-dioxygenase（IDO）,the first rate-limiting tryptophan -degrading enzyme in the kynurenine *** of this enzyme by inflammatory signals leads to an increase in the kynurenine/tryptophan ratio in plasma and the generation of neuroactive mediators,including 3- hydroxykynurenine（3-HK） and quinolinic acid（QUIN）.High levels of 3-HK and QUIN induce neuronal damage via oxidative stress and over stimulation of N-memyl-D-aspartate（NMDA） *** we investigated the mechanism of IDO expression following acute activation of the innate immune system by lipopolysaccharide（LPS） in primary cultures of microglia derived from neonatal C57BL/6 ***（10 ng/ml） induced IDO transcripts that peaked at 8 h and enzymatic activity at 24 h,resulting in an increase in extracellular kynurenine,the catabolic product of IDO-induced tryptophan *** IDO induction by LPS was accompanied by synthesis and secretion of the proinflammatory cytokines TNFαand IL-6,but without detectable IFNγ*** explore the mechanism of LPS-induced IDO expression, microglia were pretreated with the c-Jun N-terminal kinase（JNK） inhibitor SP600125 for 30 min before LPS *** found that SP600125 blocked JNK phosphorylation and significantly decreased IDO expression induced by LPS,which was accompanied by a reduction of LPS-induced expression of TNFαand ***,these data extend to microglia the property that LPS induces IDO expression v

关键词： nitric oxide indoleamine 2,3-dioxygenase lipopoly saccharide kynurenine interferon-7 primary microglia

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Evolving Models and Tools for microglial Studies in the Central Nervous System

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Neuroscience Bulletin 2021年第8期37卷 1218-1233页

作者： Yang Zhang Donghong Cui Shanghai Mental Health Center Shanghai Jiao Tong University School of MedicineShanghai200030China Shanghai Key Laboratory of Psychotic Disorders Shanghai201108China

microglia play multiple roles in such processes as brain development,homeostasis,and *** to their diverse mechanisms of functions,the complex sub-classifications,and the large differences between different species,especially compared with humans,very different or even opposite conclusions can be drawn from studies with different research *** choice of appropriate research models and the associated tools are thus key ingredients of studies on *** are the most commonly used animal *** this review,we summarize in vitro and in vivo models of mouse and human-derived microglial research models,including microglial cell lines,primary microglia,induced microglia-like cells,transgenic mice,human-mouse chimeric models,and microglial replacement *** also summarize recent developments in novel single-cell and in vivo imaging *** hope our review can serve as an efficient reference for the future study of microglia.

关键词： microglial cell lines primary microglia Induced microglia-like cells Transgenic mice Human-mouse chimeric models microglial replacement Single-cell technology In vivo imaging

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Nitrite oxide is not involved in modulation of indoleamine 2,3-dioxygenase in microglia activated with LPS plus IFNγ

Nitrite oxide is not involved in modulation of indoleamine 2...

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中国生理学会第23届全国会员代表大会暨生理学学术大会

作者： Marcus A.Lawson Robert Dantzer Keith W.Kelley College of ACES University of Illinois at Urbana-Champaign USA

Indoleamine 2,3-dioxygenase(IDO) is an intracellular heme enzyme metabolizing tryptophan along the kynurenine *** is evidence that IDO and nitric oxide synthase(NOS) pathways are *** several kinds of cells including murine macrophages,nitric oxide(NO) is a potent inhibitor of IDO,but murine microglial cell lines are *** we tested this hypothesis in primary cultures of microglia from neonatal C57BL/6J *** were activated with IFNγ(1 ng/mL) and LPS(10 ng/mL).This activation was marked by abundant expression of iNOS mRNA and NO production secreted into cells culture *** an identical time-point as iNOS,IDO mRNA and its activity were also significantly *** iNOS inhibitor,L-NIL hydrochloride (30μmol/L) did not affect expressions of iNOS mRNA,IDO mRNA and IDO activity,whereas it fully blocked the ability of IFNγand LPS to induce *** the contrary to the up-regulation of IDO activity,IFNγand LPS induced a reduction in extracellular kynurenine,the first metabolism of IDO catalyzing tryptophan along the kynurenine ***,this reduction of kynurenine in the culture medium was completely blocked by *** explore the mechanism for the reduction in kynurenine,we did cell-free experiments with exogenous kynurenine and *** results were that the level of exogenous kynurenine decreased in the presence not absence of exogenous sodium nitrite(NaNO) after deproteinization with sulfosalicylic acid solution(SSA).These data extend and establish the concept that NO does not affect the expression of IDO mRNA and its activity in primary murine microglia activated by LPS and IFNγ.Furthermore,samples are frequently deproteinized with trichloroacetic acid (TCA) or SSA before kynurenine measurement by *** nitrite degrades kynurenine under SSA condition, we need carefully think about kynurenine’s real concentration measured by HPLC,and draw a reasonable conclusion about the action of NO on IDO when nitri

关键词： nitric oxide kynurenine indoleamine 2,3-dioxygenase lipopolysaccharide interferon-gamma primary microglia

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