Suppressorofcytokinesignaling3(SOCS3)wasreportedasafeedbackinhibitorofcytokinereceptorsignalingbyinhibitingtheJAK-STATsignaltransductionpathway.Wesoughttotesttheanti-endotoxicsepticshockeffectofliposomemediatedgenedeliveryofSOCS3inalethalendotoxicshockmousemodel.BALB/cmicewereinjectedintraperitoneallywith200μgpcDNA3.1-SOCS3cationicliposomes,whilepcDNA3.1-IL-10andemptyvectoraspositiveandnegativecontrolrespectively.Forty-eighthoursaftergenedelivery,micewerechallengedwith4μgofE.coli0127:B8LPSand18mgD-GalNadministeredi.p.90minlater,serumTNF-αlevelwasdetermined.Survivaloverthenext48hwasevaluated.Peritonealmacrophagesfromsurvivalmicewerestimulatedinvitrowith1μg/mlLPSfor18h,andthesupernatantswereharvestedfordeterminationoftheamountofTNF-α.WefoundthatgenedeliveryofSOCS3significantlyincreasethemousesurvivalratefrom27.8±9.6%ofcontrolgroupto61.1±9.6%(p＜0.01).Incomparisonwithcontrolgroup(218±13pg/ml)andshamdeliverygroup(219±22pg/ml),genedeliveryofSOCS3reducedthelevelofserumTNF-α(68±9pg/ml)significantly(p＜0.01).Furthermore,genedeliveryofSOCS3displayedthecapacityofpreventionoftoleranceofperitonealmacrophagestoLPS.ThesefindingssuggestthatgenedeliveryofSOCS3mediatedbyliposomeisapromisingapproachforendotoxicsepticshocktreatment.Cellular&MolecularImmunology.
