简介：Theworkistoexploretherelationshipbetweenthelevelsofcytokines(IL-1βandIL-6)inC57BL/6JmicetreatedwithMPTPandbrainlateralization.Byusingpawpreferencetest,right-pawed,left-pawedmicemodelswereestablished.Followingsingleinjectionof1-methyl-4-pheny1-2,3,6-tetrahydropyrid(MPTP)(40mg/kg)toimpairdopaminergicneuron,enzymelinkedimmunosorbentassay(ELISA)kitswereusedfordetectionofplasmalevelsofcytokines.TheresultsshowedthatinsalinetreatedC57BL/6Jmice(control),therewasnoobviousdifferenceobservedbetweenleft-pawedandright-pawedmiceinplasmalevelsofIL-1βandIL-6.InMPTPtreatedmice,therewasnodifferencebetweenlevelofIL-1βinleft-pawedmiceandthatinright-pawedonesinstatistics,thatis,theywereincreasedonday1andday3,butdecreasedonday6.TheplasmalevelofIL-6waslowerinleft-pawedthanthatinright-pawedmice(p＜0.005)afterMPTPtreatment.Onday1andday3,thelevelofIL-6wasalmostthesameascontrol;onday6,itwassignificantlyincreased,higherthanthatofcontrol(p＜0.001)inleft-pawedmice.Whileinright-pawedmice,onday1andday3,itwasnodifferentfromcontrol,too.Andonday6,itsignificantlyincreasedincomparedwithcontrol(p＜0.005).Inconclusion,thelevelofplasmaIL-6ofC57BL/6JmicetreatedwithMPTPincreased.ThevariationofIL-6wascorrelatedtobrainlateralization.

简介：IthasbeenshownthatIL-2andIL-15canhaveopposingeffectsonlifeanddeathofTcells.However,theroleofIL-2andIL-15inregulatingthefateofothercelltypesislessclear.Inthepresentstudy,weexaminedtheimpactofIL-2andIL-15onlifeanddeathofpre-BcellsusingtheBAF-B03line.WeshowedthatBAF-B03cellsconstitutivelyexpressedtheprivateIL-2RαchainandIL-15Rαchain,andthesharedIL-2Rβchainandγcchain.StimulationofBAF-B03cellsinvitrowithIL-2andIL-15inducedvigorouscellproliferationinadose-dependentfashion.TitrationofIL-2andIL-15intheassayshowedthatthemitoticeffectsofIL-2andIL-15wereremarkablysimilar,Howerer,thesensitivitiesofBAF-B03cellstoFasmediatedapoptosisafterIL-2andIL-15stimulationwerestrikinglydifferent.CellsculturedinIL-2readilyunderwentapoptoticcelldeathuponcross-linkingoftheFasreceptorwhereascellsculturedinIL-15wereextremelyresistanttoFastriggeredcelldeath.Theanti-apoptoticeffectofIL-15inthismodelwasassociatedwithincreasedexpressionofBcl-xL.FLIPexpression,however,wascomparablebetweenIL-2andIL-15stimulatedcells.WeconcludethatIL-2andIL-15havediametricallyoppositeeffectonthefateofBAF-B03cells,althoughbothcytokinessharesimilarreceptorstructureandexhibitsimilarmitoticactivities.

简介：Quercetinisaherbalflavonoidderivedfromvariousfoodsofplantoriginandplaysaroleinanti-inflammation.Althoughanumberofresearchesinthefieldhavebeendone,themechanismofanti-inflammatoryeffectofquercetinshouldbefurtherclarified.Inthepresentstudy,weinvestigatedtheeffectsofquercetinonIL-6productionbyLPS-stimulatedneutrophilsinhuman.Neutrophilswerewerepre-treatedwithquercetinatthefinalconcentrationsofrangingfrom0-80μMfor30min,ornottreated,andthenincubatedinthepresenceorabsenceoflipopolysaccharide(LPS)atafinalconcentrationof100ng/mlforindicatedtime.ThesecretionlevelofIL-6intheculturesupernatantswasassayedbyELISA,theintracellularlevelofIL-6wasdetectedbyflowcytometryandtheexpressionofIL-6mRNAwasanalyzedbyRT-PCR.TheexperimentresultsshowedthatneutrophilsculturedwithmediumorquercetinalonedidnotexpressIL-6,butLPS(100ng/ml)inducedIL-6expressionofneutrophils.However,afterpre-treatmentofneutrophilswithquercetin(40μM)for30min,theinducibleeffectsofLPSontheincreaseofIL-6secretion,intracellularIL-6levelandIL-6mRNAexpressionbyneutrophilswereabrogated.IL-6isoneoftheimportantpro-inflammatoryfactors,especiallyinearlyphageofinflammation.Thus,ourdatasuggestedthatquercetinmightexertitsanti-inflammatoryeffectthroughnegativelymodulatingpro-inflammatoryfactors,suchasIL-6.TheinhibitoryeffectsofquercetinonIL-6productionbyneutrophilsmayprovideatheoreticalbasisonfuturetherapyofinflammation.

简介：Interleukin12(IL-12)and/orinterleukin18(IL-18)geneablatedmicewereappliedfortheinvestigationofthetissueexpressionofinterferonγ(IFN-γ).ForIL-12^-/-,IL-18^-/-,IL-12^-/-/18^-/-andwtmice,reproductiveperformancewererecordedandIFN-γconcentrationsinheart,lung,liver,spleen,kidneyandserumwerequantifiedbyELISA.TherewerenosignificantdifferencesofIFN-γ,inheart,lungandkidneybetween4strainsalthoughcontrolgroupwashigher.ItwasobservedthatforIL-12^-/-mice,comparedwithother3groups,IFN-γinliverandspleenweredecreased(p<0.05)andreproductiveperformanceappearedtobeimpaired.SerumIFN-γlevelofIL-12^-/-/18^-/-micewassignificantlyhigher(p<0.05).ItwasshowedthatIFN-γproductionsunderthenormalconditionwereindependentuponIL-12andIL-18,itsexpressionsinvarioustissuesweredifferent,andoptimalIFN-γisnecessaryforthenormalgrowthanddevelopmentofmammals.Thisstudyishelpfulforclinicalcytokinestherapy.Cellular&MolecularImmunology.2005;2(1):68-72.

简介：Interleukin-6(IL-6)-deficientmicearepronetoethanol-inducedapoptosisandsteatosisintheliver;however,theunderlyingmechanismisnotfullyunderstood.Mitochondrialdysfunctioncausedbyoxidativestressisanearlyeventthatplaysanimportantroleinthepathogenesisofalcoholicliverdisease.Therefore,wehypothesizethattheprotectiveroleofIL-6inethanol-inducedliverinjuryismediatedviasuppressionofethanol-inducedoxidativestressandmitochondrialdysfunction.Totestthishypothesis,weexaminedtheeffectsofIL-6onethanol-inducedoxidativestress,mitochondrialinjury,andenergydepletionintheliversofIL-6(-/-)miceandhepatocytesfromethanol-fedrats.Ethanolconsumptionleadstostrongerinductionofmalondialdehyde(MDA)inIL-6(-/-)micecomparedtowild-typecontrolmice,whichcanbecorrectedbyadministrationofIL-6.Invitro,IL-6treatmentpreventsethanol-mediatedinductionofreactiveoxygenspecies(ROS),MDA,mitochondrialpermeabilitytransition(MPT),andethanol-mediateddepletionofadenosinetriphosphate(ATP)inhepatocytesfromethanol-fedrats.AdministrationofIL-6invivoalsoreversesethanol-inducedMDAandATPdepletioninhepatocytes.Finally,IL-6treatmentinducesmetallothioneinproteinexpression,butnotsuperoxidedismutaseandglutathioneperoxidaseinculturedhepatocytes.Inconclusion,IL-6protectsagainstethanol-inducedoxidativestressandmitochondrialdysfunctioninhepatocytesviainductionofmetallothioneinproteinexpression,whichmayaccountfortheprotectiveroleofIL-6inalcoholicliverdisease.

简介：在血和第二等的淋巴的纸巾之间的成熟淋巴细胞的循环在免疫系统起一个中央作用。从进在高endothelial小静脉以外的第二等的淋巴的纸巾的血的淋巴细胞的Homing高度依赖于在chemokines之间的相互作用CCL19，CCL21，CXCL12，和CXCL13，和他们的受体CCR7，CXCR4和CXCR5。然而，到淋巴的从第二等的淋巴的纸巾的淋巴细胞外出的分子的机制仍然保持不清楚。我们发现了immunomodulator的一个新班，由植物的导出黄蜂的自然产品的化学修正的FTY720，ISP-I(myriocin)。FTY720被显示了在试验性的allograft和自体免疫的疾病模型高度有效。FTY720的一个惹人注目的特征是在在在这些的那项表演immunomodulating活动建模的剂量的外部血淋巴细胞的显著减少的正式就职。由FTY720的传播淋巴细胞的减小被iymphocytes的隐遁引起进第二等的淋巴的纸巾和胸腺。FTY720很快被变换成FTY720磷酸盐的(S)-enantiomer[由鞘氨醇kinase的(S)-FTY720-P]2在vivo。(S)-FTY720-P充当S1P受体类型1的有势力收缩筋(S1P1)，在淋巴细胞上导致S1P1的长期的下面规定，并且从而向S1P禁止淋巴细胞的迁居。因此，导致FTY720的淋巴细胞隐遁由它的活跃代谢物(S)-FTY720-P由于从第二等的淋巴的纸巾和胸腺的S1P/S1P1-dependent淋巴细胞外出的抑制，这被假定。在整个FTY720的行动的机制的分析，S1P/S1P1相互作用从第二等的淋巴的纸巾和胸腺为淋巴细胞外出起一个重要作用，这被澄清。

简介：TodeterminetheregulatoryeffectsofestrogenandcytokineIL-6andIL-8onthegrowthofepithelialovariancancer(OVCA),wefirstexaminedthestatusofestrogenreceptors(ERαandERβ),IL-6receptor(IL-6Rαandgp130),andIL-8receptor(IL-8RAandIL-8RB)onfiveepithelialOVCAcelllinesbysemiquantitativeRT-PCRandWesternblotanalysis.Resultsshowedthattheexpressionsofthesereceptorswerevariableonthefivecells.ThoseOVCAcellsexpressingthereceptorswereselectedtostudyrelatedmolecularmechanism.MTTassaywasperformedtoobservetheeffectsof17β-estradiol(E2),IL-6andIL-8oncellproliferation.WediscoveredthatE2markedlypromotedtheproliferationofCAOV-3andOVCAR-3cellinatime-anddose-dependentmanner.Tamoxifen(Txf),anERinhibitor,completelyblockedtheproliferationoftheE2-inducedcells,andIL-6-or/andIL-8-neutralizingantibodyonlyshowedpartiallyblockingactivity.IL-6andIL-8wereabletosignificantlystimulateCAOV-3andOVCAR-3cellproliferationinatime-anddose-dependentmanner,whichhadapotentialsynergisticeffectonCAOV-3cellsbutnotonOVCAR-3cells.Thecellproliferationinducedbythesetwocytokineswasabolishedcompletelybytheirspecificneutralizingantibodies,partiallybyTxf,butnotbyunrelatedgoatIgG.Takentogether,ourresultssuggestedthatestrogen,IL-6andIL-8couldmodulateOVCAgrowthbyformingareciprocalcascadewithamplifyingeffect.Cellular&MolecularImmunology.

简介：包括长期的感染，自体免疫的疾病和癌症，很长期的人的疾病的致病经常包含坚持的、未解决的煽动性的回答。决定尖锐煽动性的回答的变换进一个长期的过程的分子的机制难倒研究人员许多年了。最近的研究揭示那B7-H1(CD274，PD-L1)，一个最新识别的co-stimulatory分子，拥有天真的T房间的合作刺激和激活的受动器T房间的抑制的双功能。异常细胞的表示和B7-H1的deregulated功能在长期的病毒、细胞内部的细菌的感染期间被报导了，以及在许多自体免疫的疾病和癌症。重要地，B7-H1的双功能的解除管制看起来与被联系一延长，由为激活诱惑天真的T房间并且阻抑的不完全的有免疫力的反应激活受动器T房间。而且，指向B7-H1信号的策略的开发提供一条新、有希望的途径操作与长期的发炎联系的破坏疾病。因此，B7-H1可以在煽动性的回答的慢性起一个批评immunoregulatory作用。

简介：规划death-1(PD-1)，CD28家庭的一个成员，能否定地调整TCR由与它的血缘的ligands(PD-L1或PD-L2)交往的开始建筑群的发信号。PD-1/PD-L1小径起一个重要作用在下面调整适应有免疫力的回答的有效阶段和这条小径的封锁被证明提高抗病毒并且antitumoral免疫，建议让治疗的发展与病毒感染或恶意在病人改进T房间回答可能是一个潜在的目标。在现在的学习，有一个carboxyl终端他的标签的人的PD-1的细胞外的域(指定了为sPD-1)在Escherichiacoli被表示为包括身体。产品是在列上refolded，由使不能调动的金属亲密关系层析净化了，并且由西方的弄污描绘了。而且，有高纯净的可溶的PD-1与它的血缘的ligandPD-L1拥有了特定的有约束力的活动，并且分离常数是由Scatchard情节分析决定了的0.43nmol/L。这些结果建议从原核生物的房间的refoldedsPD-1可能具有对提高抗病毒和antitumoral免疫者回答的治疗学的兴趣。

简介：生来的杀手(NK)房间是骨头导出髓的淋巴细胞。他们生产cytokines调整获得的免疫的发展。鉴于他们在母亲胎儿的接口的累积，子宫的生来的杀手(uNK)房间也被认为在怀孕期间起必要作用。我们的结果在子宫的子宫内膜，肝，怒气和外部血由NK房间比较了cytokine分泌物侧面的差别，并且由uNK房间集中了于cytokines分泌物。在怀孕鼠标的子宫的子宫内膜的IFN-和TNF-的表达式是比在肝的那些低的，这被表明，但是他们在怀孕期间显著地增加。我们的学习证明uNK房间的数字在怀孕期间显著地被增加。他们比另外的导出器官的NK房间，和他们也分泌IL-4和IL-5的次要的数量的生产了更多的IFN-和TNF-。结果显示uNK房间生产的IFN-和TNF-保证了成功的怀孕进步。

简介：在维持平衡外部有免疫力的system.Recent的一个重要角色学习的CD4+CD25+规章的T(TR)房间玩证明了TR房间可以也在压制反肿瘤免疫者反应起一个关键作用。以便调查TR极化上的肿瘤免疫者微型环境和它的影响，糟糕产生免疫性的肿瘤房间线D5(C57BL/6，H-2b)，产生免疫性的肿瘤房间线FBL3(C57BL/6，H-2b)并且H22BALB/c，H-2d)被用来建立syngeneic/allogeneic，糟糕产生免疫性/产生免疫性的混合淋巴细胞肿瘤房间文化(MLTC)。我们的结果表明在告知的splenocytes与D5肿瘤房间刺激了的syngeneic的MLTC的CD4+CD25+T房间的比例与H22房间比那高(0.43%对0.044%，并且类似的结果在与.Thesplenocytes从更高表明的房间比从D5肿瘤的allogeneicMLTC，房间，和splenocytes刺激了机智的CD4+CD25+房间分配的D5肿瘤的syngeneicMLTC与上层清液刺激了的D5肿瘤房间(0.39%对0.04%)刺激的allogeneicsplenocytes出现了TGF-1和Th2面向的cytokines(IL-4和IL-10)在糟糕产生免疫性的肿瘤房间的syngeneicMLTC的上层清液被统治。我们的结果为学习位于肿瘤免疫者监视下面的机制以及为肿瘤免疫疗法提供了有用信息。

简介：到病原体的暴露导致象巨噬细胞那样的介绍抗原的房间(APC)和树枝状的房间(DC)生产各种各样的内长的调停人，包括导出的arachidonic酸(AA)eicosanoids，cytokines，和氮的氧化物(没有)。激活的APC的许多分泌产品能以一种autocrine方式自己行动并且调制他们的功能。而且，在内长的bioactive分子之间跨相互作用为他们激活并且支撑有免疫力、煽动性的回答，并且调整有免疫力的动态平衡的能力与重要后果调整职业APC的函数。尽管为许多忽视了什么时候的年与他们在心血管的动态平衡，癌症和发炎的角色相比，在免疫学的eicosanoids的重要性正在变得更多定义。前列腺素(PG)的角色E2(PGE2)，知道的最好和大多数之一很好学习了eicosanoids，具有特别兴趣。它由对他们分泌cytokines的区别，成熟和他们的能力起作用调制职业DC的活动。特别地在造血的cytokines之中，interleukin-10(IL-10)是显示immunostimulatory和immunoregulatory活动的一个多种的分子。因为它的反煽动性的性质，IL-10依附许多注意。它由myeloid起源的房间调制cytokines，可溶的调停人和房间表面分子的表示，特别地巨噬细胞和DC。我们以前报导PGE2是在骨头的IL-10的有势力inducer导出髓的DC(BM-DC)，和导致PGE2的IL-10是BM-DC支持inflammatory显型的一个关键管理者。BM-DC可以被看作一个重要模型学习在内长的调停人之间的复杂相互作用，并且autocrineIL-10在导出AA的类脂化合物调停人，的crossregulation起一个枢轴的作用cytokines，并且没有，与有免疫力、煽动性的回答上的批评效果。细胞与分子的免疫学。2006；3(4):271-277。

简介：高血压生产为与疾病联系的死亡经常负责的pathophysiological变化。overactive高血压蛋白原酶血管收缩素系统在高血压和与高血压联系的目标机关损坏的发展起一个中央作用，是明显的。我们以前发现了新奇血管收缩素受体(AT1)vaccine-ATR12181在自发地高血压的老鼠(SHR)稀释了高血压(BP)的发展人的必要高血压的模型。我们的目的是决定高BP的这变细是否与由高血压的状态导致的目标机关损坏的预防被联系。SHR被在联合复杂的peptide-tetanus-toxoid的重复下的注射与Freund的助手从AT1A受体的extracelluar部分对肽(编码ATR12181)使免疫。64个星期长期的观察被执行。重复种痘导致了anti-ATR12181抗体的正式就职。在观察的结束，种牛痘表明的SHR降低肾损害的BP，减少的心脏的肥大和变细。在心和肾的c-fos和c-jun的mRNA层次在种牛痘的SHR被减少。因为自我抗原被使用，疫苗的安全被担心。然而，自体免疫的疾病的符号没在心和肾的节被观察。这些数据证明对AT1受体的细胞外的部分的域的那重复免疫能对高血压引起一个目标机关保护。对AT1受体的活跃免疫可以在高血压的治疗被看作有希望的新策略。

简介：FTY720,asphingosine1-phosphatereceptormodulator,inducesamarkeddecreaseinthenumberofperipheralbloodlymphocytesandexertsimmunomodulatingactivityinvariousexperimentalallograftandautoimmunediseasemodels.Inthisstudy,weevaluatedtheeffectofFTY720anditsactivemetabolite,(S)-enantiomerofFTY720-phosphate[(S)-FTY720-P]onexperimentalautoimmuneencephalomyelitis(EAE)inratsandmice.ProphylacticadministrationofFTY720at0.1to1mg/kgalmostcompletelypreventedthedevelopmentofEAE,andtherapeutictreatmentwithFTY720significantlyinhibitedtheprogressionofEAEandEAE-associatedhistologicalchangeinthespinalcordsofLEWratsinducedbyimmunizationwithmyelinbasicprotein.ConsistentwithratEAE,thedevelopmentofproteolipidprotein-inducedEAEinSJL/JmicewasalmostcompletelypreventedandinfiltrationofCD4+TcellsintospinalcordwasdecreasedbyprophylactictreatmentwithFTY720and(S)-FTY720-P.WhenFTY720or(S)-FTY720-PwasgivenafterestablishmentofEAEinSJL/Jmice,therelapseofEAEwasmarkedlyinhibitedascomparedwithinterferon-β,andtheareaofdemyelinationandtheinfiltrationofCD4+TcellsweredecreasedinspinalcordsofEAEmice.SimilartherapeuticeffectbyFTY720wasobtainedinmyelinoligodendrocyteglycoprotein-inducedEAEinC57BL/6mice.TheseresultsindicatethatFTY720exhibitsnotonlyaprophylacticbutalsoatherapeuticeffectonEAEinratsandmice,andthattheeffectofFTY720onEAEappearstobeduetoareductionoftheinfiltrationofmyelinantigen-specificCD4+Tcellsintotheinflammationsite.

简介：39Vibriocholerae的一个总数非，非，O139拉紧的O1从Dhaka城市的不同部分的表面水被孤立，孟加拉国。，显示出的这些种类ctx或zot基因缺乏的所有由PCRanalysis.Eighteen代表证明种类为enterotoxin生产使用被测试一个兔子ileal环模型，哪个生活8个种类和文化的房间6个种类过滤在ileal的生产液体累积循环。然而，任何一个都没他们生产热马厩毒素(圣)，由乳臭未干的老鼠试金检测了。在另一方面，中的15%个孤立由中国仓鼠卵巢(CHO)房间试金检测了的生产细胞毒素。乘集中的文化的五十紧张没对反霍乱毒素给任何沉淀素乐队的代表过滤，建议紧张生产了enterotoxin，它与已知的霍乱毒素(CT)antigenically不同。百分之八十个总数孤立被发现为易变的haemolysin由试管方法检测了的热积极，而，39%被Christie-Atkins-Munch-Petersen(营地)方法发现积极。然而，87%isolates是积极的因为紧张的haemagglutinin/protease和所有为mannose-sensitive-haemagglutinin试金是积极的。

简介：Directintratumoralintroductionoftherapeuticorregulatorygenesisadevelopingtechnologywithpotentialapplicationforcancergenetherapy.Macrophageinflammatoryprotein-1beta(MIP-1β)isachemokinewhichcanchemoattractimmunecellssuchasTcells.Inthepresentstudy,murinecolorectaladenocarcinomaCT26cellsweretransfectedwitharecombinantadenovirus(AdhMIP-1β)carryingthehumanMIP-1βgene.24hpost-transfection,hMIP-1βlevelsreachedapproximately980pg/mlinsupernatantsof106hMIP-1β-transfectedCT26cells.Moreover,thesupernatantsexhibitedchemotacticactivityforCD8+Tcells,CD4+Tcells,NKcellsandimmatureDCs.IntratumoralinjectionofAdhMIP-1βsignificantlyinhibitedtumorgrowthandprolongedthesurvivaltimeoftumor-bearingmice.IntratumoralhMIP-1βgenetransferalsoinducedpowerfultumor-specificCTLresponsesinvivo.ThetherapeuticeffectsofhMIP-1βgenetherapyweregreatlyreducedfollowinginvivodepletionofbothCD4+andCD8+Tcells,butwereunaffectedbydepletionofsingleTcellsubsets.ImmunecelldepletionexperimentsalsorevealedthatNKcellsplayedanimportantroleinhMIP-1β-inducedantitumorresponses.TheseresultssuggestthatintratumoralexpressionofhMIP-1βhasthepotentialeffecttoinducehostantitumorimmunityandmayprovetobeausefulformofcancergenetherapy.