摘要
AIM:Toinvestigateifanimmuneimbalancemayaccountforthedevelopmentandprogressionofchronicradiationenteritis.WeanalyzedtheTh1/Th2immuneresponseprofileearlyand6moafterfractionatedcolorectalirradiation.METHODS:Aratmodeloffractionatedcolorectalγ-irradiation(4-Gyfractions,3fractionsperweek)wasdesignedtoinvestigatetheeffectsofcumulativedoseoninflammatorymediators(cytokinesandchemo-kines)andimmuneresponse(Th1/Th2profileandim-munosuppressivemediatorIL-10)duringacute(early)responseand6moaftertheendoffractionatedirradia-tion(chronicresponse).Analyseswereperformed1dafterthecumulativedosesof16Gyand36Gyand1d,3d,and26wkafterthecumulativedoseof52Gy.RESULTS:Withoutcausinghistologicaldamage,fractionatedradiationinducedelevatedexpressionofIL-1β,TNFα,MCP-1,andiNOSindistalcolonicmucosaduringtheearlypost-irradiationphase.Atthattime,aTh2profilewasconfirmedbyexpressionofboththeTh2-specifictranscriptionfactorGATA-3andthechemokinereceptorCCR4andbysuppressionoftheTh1cytokineIFNγ/IP-10throughouttheirradiationprotocol.After6mo,despitethe2-foldreductionofiNOSandMCP-1levels,theTh2profilepersisted,asshownbya50%reductionintheexpressionoftheTh1transcriptionfactorT-bet,thechemokinereceptorCCXCR3,andtheIFNγ/STAT1pathway.Atthesametime-point,theimmuno-suppressiveIL-10/STAT3pathway,knowntoregulatetheTh1/Th2balance,wasexpressed,inirradiatedrats,atapproximatelyhalfitslevelascomparedtocontrols.ThissuppressionwasassociatedwithanoverexpressionofSOCS3,whichinhibitsthefeedbackoftheTh1polarizationandregulatesIL-10production.CONCLUSION:ColorectalirradiationinducesTh2polarization,defectiveIL-10/STAT3pathwayactivationandSOCS3overexpression.Thesechanges,inturn,maintainaimmunologicalimbalancethatpersistsinthelongterm.
出版日期
2008年12月22日（中国期刊网平台首次上网日期，不代表论文的发表时间）
