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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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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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迅速组织疫苗的生产

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流程工业 2008年第4期 52-53页

作者： marcus Tronich lawson软件公司

统一、集成式的ERP解决方案将一家大型免疫药品生产厂带入到了整个供应链之中。同时，该方案也支持产品的可追溯性，保证了疫苗生产遵守所有的技术规范要求。

关键词：疫苗生产生产厂组织免疫药品可追溯性供应链 ERP 集成式

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