简介:Modulationbybalancingactivatingandinhibitoryreceptorsconstitutesanimportantmechanismforregulatingimmuneresponses.Cellsthatareactivatedfollowingligationofreceptorsbearingimmunoreceptortyrosine-basedactivationmotifs(ITAMs)canbenegativelyregulatedbyotherreceptorsbearingimmunoreceptortyrosine-basedinhibitionmotifs(ITIMs).Humanmastcells(MCs)arethemajoreffectorcellsoftypeIhypersensitivityandimportantparticipantsinanumberofdiseaseprocesses.Antigen-mediatedaggregationofIgEboundtoitshigh-affinityreceptoronMCsinitiatesacomplexseriesofbiochemicaleventsleadingtoMCactivation.WithgreatdetaileddescriptionandanalysisofseveralinhibitoryreceptorsonhumanMCs,acentralparadigmofnegativeregulationofhumanMCactivationbythesereceptorshasemerged.Cellular&MolecularImmunology.2004;1(6):408-415.
简介:Icariin,themajoractivecomponentofChinesemedicinalherbepimediumbrevicornummaxim,isusedwidelyintraditionalChinesemedicineforthetreatmentofneurologicaldiseases.However,theeffectsoficariinonmyelininhibitoryfactorsareasyetunclear.Inthepresentstudy,administrationoficariinat20mg/kgshowedamarkedreductioninneurologicaldeficitofmiddlecerebralarteryocclusionrats.Icariinexhibitedbetterinhibitoryeffectsonmyelininhibitoryfactors:Nogo-A,myelin-associatedglycoproteinandoligodendrocytemyelinglycoproteininischemiaregionsofmiddlecerebralarteryocclusionratscomparedwithmonosialotetrahexosylganglioside.Theseresultsindicatethaticariinexhibitspotentinhibitoryeffectsonexpressionofmyelininhibitorsaftermiddlecerebralarteryocclusion-inducedfocalcerebralischemiainvivo.Thiseffectmaybemediated,atleastinpart,bytheinhibitionofbothNogo-A,myelin-associatedglycoproteinandoligodendrocytemyelinglycoproteinactivation,followedbytheenhancementofaxonalsproutingandregeneration,resultinginneurologicalfunctionalrecovery.
简介:在土壤的芳香的混合物(交流)能为土壤NH3氧化导致竞争抑制,并且氮的硝化作用禁止者能习惯于这个目的。一个实验室孵化实验与12nitroaromatic混合物(NAC)被执行,15amidoaromatic混合物(AAC)和20hydroxyaromatic混合物(HAC)到在土壤上估计交流的禁止的效果氮的硝化作用。把结果基于这些,交流的批评、最佳的集中为更好禁止的效果被决定。大多数测试交流能禁止土壤氮的硝化作用;有效性与土壤类型不同。在交流之中,有m-nitryl的NAC,氨基或与芳香的戒指上或与p氢氧根的一个nitro组或一个氯原子一起的氢氧根和AAC是更有效的。3硝基苯胺,4-aminophenol和3-nitrophenol作为氮的硝化作用禁止者显示出最大的潜力。在棕色的土壤和黄棕色土壤的这些混合物的批评集中被发现是0.5mgkg?1土壤。由于交流的毒性,致癌性和mutagenicity,进一步毒物学并且在交流在农业、园艺的惯例被用作氮的硝化作用禁止者以前,ecotoxicological研究是必要的。
简介:为阐明β榄香烯的抗血小板作用,本文分别采用比浊法和放免法测定大鼠连续ip7dβ榄香烯乳6.25~12.5mg·kg-1·d-1后对血小板聚集、血浆ketoPGF1α和TXB2水平的影响。结果表明,本品分别使凝血酶、花生四烯酸和ADP诱导血小板最大聚集率下降38.3%~42.6%,14.7%~19.1%和7.2%~10.8%,血浆TXB2从88ng·L-1下降至72ng·L-1,ketoPGF1α从17.5ng·L-1增加至20.9ng·L-1。提示TXB2降低和ketoPGF1α值增加是其抑制血小板聚集的作用机制之一。
简介:房间有大量的控制维持他们的完整并且阻止随机切换到另外一个一个生物状态。RafKinase禁止的蛋白质(RKIP),phosphatidylethanolamine绑定蛋白质(PEBP)的一个成员家庭,表明工作维持“yinyang”或生物系统的平衡的串联的调节的人的一个新类是代表性的。RKIP禁止地图kinase(Raf-MEK-ERK),表明串联的G联合蛋白质的受体(GPCR)kinase和NFkappaB。因为RKIP指向依赖于它磷酸化的状态的不同家族ases,RKIP也行动集成多重环境刺激开始的串音。RKIP的损失或弄空导致正常细胞的壅滞和罐头的混乱导致象癌症那样的chromosomal畸形和疾病状态。因为RKIP和PEBP家庭以前被考察了,这分析的目标是提供更改并且加亮一些RKIP的唯一的特征在细胞的发信号的过程的规定使它成为一个批评播放器。
简介:Toinvestigatetheeffectsofantisenseoligonucleotidesontheexpressionofmacrophagemigrationinhibitoryfactor(MIF)onmacrophages,themousephosphorothioateoligonucleotidesweredesignedandsynthesizedwiththesequencesofantisense,5'-TACGGATACAAGTAGCAC-3';Sense,5'-ATGC-CTATGTTCATCGTG-3';Missense,5'-CTCTCAGACTCGATCTGT-3'.Thesephosphorothioateoligonucleotideswerethentransfectedintoculturedmacrophages(RAW264.7)byluciferasevector,andthetransfectedmacrophageswereincubatedwithLipopolysaccharide(LPS)(1ng/ml)forvariousperiodsoftimesandcollectedafterwards.ThecontentofMIFproteinintheculturalsupernatantswasdeterminedbyELISA,cellularRNAextractedandtheexpressionofMIFmRNAwasexaminedbyRT-PCRanalysis.TheexperimentalresultsshowedthatLPScouldinduceatime-dependentspecificexpressionofMIFonmacrophages,inwhichtheMIFmRNAincellsandtheMIFproteininculturalsupernatantsappearedafter3handreachedtheirhighestconcentrationat9-12hafterLPSstimulation.ThelevelsofmRNAandproteinsinthemacrophagestreatedwithantisenseolignucleotidesweredecreasedsignificantlyafterstimulationwithLPSincomparisonwiththatofstimulationwithLPSaloneorwiththatwithLPSplussenseormissenseoligonucleotides.TherewerenodifferencesamongthosewithoutLPSstimulation.ItisconcludedthatmacrophagesstimulatedwithLPSexpressMIF,andtheantisenseolignucleotidesofMIFinhibittheexpressionofMIFmRNAaswellasthesecretionofMIFproteinsinmacrophages.
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.
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简介:四新triterpenesaponins,和五已知的混合物(5-9),mandshunosidesF-I(1-4)从铁线莲mandshurica的根和根茎被孤立。他们的结构根据分光镜的证据和水解作用产品被阐明。Bisdesmosidicsaponin(3-9)在51.3%-的范围与抑制比率显示出没有生产的谦虚抑制64.6%在50摩尔
简介:BandTlymphocyteattenuator(BTLA),identifiedasanimmuneinhibitoryreceptorrecently,playswidespreadrolesonTandBcells.EmergingevidencehasgeneratedplentifulinformationonthemechanismswhichBTLAmediatesnegativeregulationinimmuneresponsesandinvolvesinavarietyofphysiologicalandpathologicalprocesses.TheexplorationofthebiologicalmechanismsandregulationofBTLAwillopenpossibilitiesonnoveltherapeuticstrategiesinimmune-relateddiseases.
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简介:ObjectivesTheeffectsofcarvediloloncalciumcurrent(ICa)wereinvestigatedinisolatedadultratventricularmyocytes.MethodsICawasrecordedbyusingwhole-cellpatch-clamprecordingtechnique.ResultsCarvedilolreversiblyinhibitedICainaconcentration-dependentmanner,carvedilolat0.1,0.3,1and10μmol/LintheextracellularsolutiondecreasedpeakICaby1.52%,18.04%,37.34%and72.18%,respectively.Thesteady-stateinactivationcurveofICawasshiftedtomorenegativepotentials,whiletheactivationcurvewasnotaltered.Therecoveryfrominactivationwasshiftedtorightdirection,itcouldnotberecoveredcompletely.Inaddition,Pretreatmentofventricularmyocyteswithprazosinandpropranololcouldn'tblockthecarvedilol-inducedreductionofICa.ConclusionsCarvedilolinhibitsICainadultratventricularmyocytesbymechanismsinvolvingpreferentialinteractionwiththeinactivatedstateofcalciumchannel.
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简介:Inthepresentstudy,weconstructedalentivirus,FIV-CMV-GFP-miR-7-3,containingthemicroRNA-7-3geneandthegreenfluorescentproteingene,andusedittotransfecthumangliomaU251cells.Fluorescencemicroscopyshowedthat80%ofU251cellsexpressedgreenfluorescence.Real-timereversetranscriptionPCRshowedthatmicroRNA-7-3RNAexpressioninU251cellswassignificantlyincreased.ProliferationwasslowedintransfectedU251cells,andmostcellswereintheG1phaseofthecellcycle.Inaddition,theexpressionoftheserine/threonineproteinkinase2wasdecreased.ResultssuggestedthattransfectionwithalentiviruscarryingmicroRNA-7-3caneffectivelysuppressepidermalgrowthfactorreceptorpathwayactivityinU251cells,arrestcellcycletransitionfromG1phasetoSphaseandinhibitgliomacellgrowth.
简介:Themainapproachtoreducegraftrejectionhasbeenfocusedonthedevelopmentofimmunosuppressiveagentsatpresent.Althoughthesestrategieshavereportedlyreducedgraftrejection,therehasbeenareciprocalincreaseinmoresevereimmunosuppressionandlethalinfections,aswellasseveresideeffects.BlockadeofcostimulatoryTcellresponsehasbeenprovedasoneofusefulstrategiestoreducegraftrejection.Furthermore,ithasbeenshownthatinfusionofdendriticcells(DCs)withapotentnegativeregulatoryabilityforTcellscouldprolongallograftsurvival.InthisstudymouseDCs(mDCs)weretransfectedwiththerecombinantplasmidpcDNA3.0containingmouseinduciblecostimulator-Ig(mICOS-Ig)cDNAbyelectroporation.ThetransientexpressionofmICOS-IginmDCcouldbedetectedbyELISAandSDS-PAGE.MouseICOS-IgfusionproteinexpressedinmDCandmICOS-Iggene-modifiedmDCcouldinhibitlymphocyteproliferationinmixedlymphocyteculture(MLC)invitro.Furthermore,mICOS-Iggene-modifiedmDCcouldinhibitlymphocyteproliferationinrecipientmice.TheseresultssuggestedthatmICOS-Iggene-modifiedmDCexertedinhibitoryeffectsonTcells,andmightbesuitablefortreatmentorpreventionofgraftrejectionandimmunopathologicdiseases.