《Prognoses of patients with acute-on-chronic hepatitis B liver failure are closely associated with altered SOCS1 mRNA expression and cytokine production following glucocorticoid treatment.》.pdf

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《Prognoses of patients with acute-on-chronic hepatitis B liver failure are closely associated with altered SOCS1 mRNA expression and cytokine production following glucocorticoid treatment.》.pdf

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CellularMolecularImmunology(2014)11．396-404 @2014CSIandUSTC．Allrightsreserved1672-7681／14$32．O0 www．nature．com／cm RESEARCHARTICLE Prognosesofpatientswithacute-·on--chronichepatitisB liverfailurearecloselyassociatedwithalteredSOCS1 mRNAexpressionandcytokineproductionfollowing glucocorticoidtreatment jina—junZhang1,Yu—ChenFan2，Ze-HuaZhao，YangYnag，Cheng—YunDou，ShuaiGao andKaiW na g2 Suppressorofcytokinesignaling(SOCS)1playsacruciaIroleintheimmuneresponseandmightcontributetothe prognosesofliverfailuretreatedwithglucocorticoid．Werecruited47acute．on．chronichepatitisBIiverfailure(ACHBLF) patientsreceivingglucocorticoidtreatmentand30healthycontrolstodeterminethepotentiaIe什ectsofglucocorticoid onthetranscriptiOnaIIeveIofSDl[．sJinperipheralbloodmononuclearcells．Onthethirdandtwenty-eighthdaysof gIucOcOrtic0idtreatment，SDCS1expressionwasnegativelycorrelatedwithmodelforend．stageIiverdisease(MELD) score．1nterleukin-6(IL-6)andtumor-necrosisfactor．ot(TNF． levelswerestatisticallylower。whiletheSOCS】 transcriptionleve1washigherinsurvivorsthannon．survivorsbothinpre．andpost．treatmentACHBLFpatients．The methylationrateoftheSDCS1promoterinACHBLFpatientswashigherthaninhealthycontrolpatientsasdeterminedby methylation-specificpolymerasechainreaction．ThemRNAleveIofS0CS1inmethylatedpromoterswassignificantly Iowerthanfr0m patientswithunmethylatedS0CS1promoters．interferon(IFN)叫．responsiveandSTAT1．dependent geneexpressionwashigherinsurvivorsandwasdramaticallydecreasedwithrisingexpressionofSDcS1after glucOc0rticOidtreatment．Mortalityratesweresignificantlyhigherinmethylatedpatientsthanforthosewithout methylationattheendofa90-dayfollow．up．Furthermore．wefoundthatfiveinsixsurvivingpatientsdisplayed demethylatedSDCS1onthetwenty—eighthdayaftertreatment．whilethatnumberwas3in10inthenon-survivors．These findingssuggestedthatACHBLFpatientswithoutS0CS1methylationmayhaveafavorableresponsetocorticoste