简介：AIDSassociatedmalignancies(ARL)isamajorcomplicationassociatedwithAIDSpatientsuponimmunosuppression.Chronicallyimmunocompromisedpatientshaveamarkedlyincreasedriskofdevelopinglymphoproliferativedisease.Intheeraofpotentantiretroviralstherapy(ARV),themalignantcomplicationsduetoHIV-1infectionhavedecreasedindevelopednationswhereARVisadministered,butstillposesamajorproblemindevelopingcountrieswhereHIV-1incidenceishighandARVisstillnotyetwidelyavailable.EveninARVtreatedindividualsthereisaconcernthattheprolongedsurvivalofmanyHIV-1carriersislikelytoeventuallyresultinanincreasednumberofmalignanciesdiagnosed.MalignanciesthatwerefoundtohavehighincidenceinHIV-infectedindividualsareKaposi'ssarcoma(KS),Hodgkin'sdisease(HD)andnon-Hodgkin'slymphoma(NHL).TheincidenceofNHLhasincreasednearly200foldinHIV-positivepatients,andaccountsforagreaterpercentageofAIDSdefiningillnessintheUSandEuropesincetheadventofHAARTtherapy.TheseAIDSrelatedlymphomasaredistinctfromtheircounterpartsseeninHIV-1seronegativepatients.ForexamplenearlyhalfofallcasesofARLareassociatedwiththepresenceofagammaherpesvirus,EpsteinBarrvirus(EBV)orhumanherpesvirus-8(HHV-8)/Kaposi'ssarcomaassociatedherpesvirus(KSHV).ThepathogenesisofARLsiscomplex.B-cellproliferationdrivenbychronicantigenemiaresultingintheinductionofpolyclonalandultimatelymonoclonallymphoproliferationmayoccurinthesettingofsevereimmunosuppression.

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简介：Thl-responseplaysacrucialroleindeterminingpathogenesisoforgan-specificautoimmunediseases.ItisbelievedthatbothIL-12andINF-αareinitiatorstoregulateTh1-response.Inourexperimentalautoimmuneuveitis(EAU)model,bothLewisandFischer344ratssharethesameMHCclassⅡImolecules,whileLewisratisEAUsusceptibleandFischer344ratisEAUresistant.However,underthesameconditionofimmunization,ifpertussistoxin(PTX)wasinjectedintraperitoneallyasanadditionaladjuvant,Fischer344ratcandevelopEAU.InthisstudyweinvestigatewhichmechanismsareinvolvedintheinductionofEAUinCFA+R16+PTX-treated(CRP-treated)Fischer344rats.InvivoandinvitrodatademonstratedthatThl-cytokine,IFN-γmRNAexpressionwassignificantlyincreasedindiseasetargettissue-eyesandindraininglymphnodecellsofCRP-treatedFischer344rat.WhenIL-12andIFN-αmRNAexpressionwerecomparedintheexperimentalgroups,onlyIFN-αmRNAexpressionwasassociatedwithEAUdevelopment.TodistinguishthesourcesofIFN-αproducingcells,itwasobservedthatIFN-αexpressionwasmainlyproducedbymacrophages.ItwasfurtherconfirmedthatnormalmacrophagefromFischer344ratwasabletoproducesignificantIFN-αinthepresenceofPTX.ThedatastronglysuggestedthatIFN-αmightbeinvolvedininitiatingThl-celldifferentiationandinturncontributetotheinductionofEAU.HighIFN-αexpressioninducedbyPTXmayrepresentanovelpathwaytoinitiateThlresponseinFischer344rat.

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简介：IL-16isaligandandchemotacticfactorforCD4+Tcells.IL-16inhibitstheCD3mediatedlymphocyteactivationandproliferation.TheeffectsofIL-16onthetargetcellsaredependentonthecelltype,thepresenceofco-activatorsetc.TounderstandtheregulationfunctionandmechanismofIL-16ontargetcells,weuseda130a.a.recombinantIL-16tostudyitseffectsonthegrowthofJurkatTleukemiacellsinvitro.WefoundthattherIL-16stimulatedtheproliferationofJurkatcellsatlowdose(10^-9M),butinhibitedthegrowthofthecellsathigherconcentration(10^-5M).Resultsshowedthat10^-5MofrIL-16treatmentinducedanenhancedapoptosisinJurkatcells.ThetreatmentblockedtheexpressionofFasL,butup-regulatedthec-mycandBidexpressioninthecells.Pre-treatmentofPKCinhibitororMEK1inhibitormarkedlyincreasedordecreasedtherIL-16inducedgrowth-inhibitingeffectsonJurkatcells,respectively.TheresultssuggestedthattherIL-16mightbearegulatorforthegrowthorapoptosisofJurkatcellsatadose-dependentmanner.Thegrowth-inhibitingeffectsofrIL-16mightbeFas/FasLindependent,but,associatedwiththeactivationofPKC,up-regulatedexpressionofc-MycandBid,andtheparticipationoftheERKsignalpathwayinJurkatcells.

简介：CT120,anovelmembrane-associatedgeneimplicatedinlungcarcinogenesis,waspreviouslyidentifiedfromchromosome17pl3.3locus,ahotmutationspotinvolvedinhumanmalignancies.Inthepresentstudy,wefurtherdeterminedthatCT120ectopicexpressioncouldpromotecellproliferationactivityofNIH3T3cellsusingMTSassay,andmonitoredthedownstreameffectsofCT120inNIH3T3cellswithAtlasmousecDNAexpressionarrays.Among588knowngenes,133geneswerefoundtobeupregulatedordownregulatedbyCT120.Twomajorsignalingpathwaysinvolvedincellproliferation,cellsurvivalandanti-apoptosiswereoverexpressedandactivatedinresponsetoCT120:OneistheRaf/MEK/ErksignalcascadesandtheotheristhePI3K/Aktsignalcascades,suggestingthatCT120mightcontribute,atleastinpart,totheconstitutivelyactivationofErkandAktinhumanlungcanercells.Inaddition,sometumormetastasisassociatedgenescathepsinB,cathepsinD,cathepsinL,MMP-2/TIMP-2werealsoupregulatedbyCT120,uponwhichCT120mightbeinvolvedintumorinvasivenessandmetastasis.Inaddition,CT120mightplayanimportantroleintumorprogressionthroughmodulatingtheexpressionofsomecandidate“LungTumorProgression”genesincludingB-Raf,Rab-2,BAX,BAG-1,YB-1,andCdc42.