Hydrodynamic Gene Delivery of Interleukin-22 Protects the Mouse Liver from Concanavalin A-, Carbon Tetrachloride-,and Fas Ligand-Induced Injury via Activation of STAT3

摘要

＜正＞ Interleukin-22 （IL-22） is a recently identified T cell-derived cytokine whose biological significance remainsobscure.Previously,we have shown that IL-22 plays a protective role in T cell-mediated hepatitis induced byConcanavalin A （Con A）,acting as a survival factor for hepatocytes.In the present paper,we demonstrate thathydrodynamic gene delivery of IL-22 cDNA driven either by a liver-specific albumin promoter or a humancytomegalovirus （CMV） promoter results in IL-22 protein expression,STAT3 activation,and expression ofseveral anti-apoptotic proteins,including Bcl-xL,Bcl-2,and Mcl-1 in the liver.Immunohistochemical analysisreveals that IL-22 protein expression is mainly detected in the cytoplasm of hepatocytes.Overexpression ofIL-22 by hydrodynamic gene delivery significantly protects against liver injury,necrosis,and apoptosis inducedby administration of Con A,carbon tetrachloride （CCl4）,or the Fas agonist Jo-2 mAb.Western blot analysesshow that overexpression of IL-22 significantly enhances activation of STAT3 and expression of Bcl-xL,Bcl-2,and Mcl-1 proteins in liver injury induced by Con A.In conclusion,hydrodynamic gene delivery of IL-22protects against liver injury induced by a variety of toxins,suggesting the therapeutic potential of IL-22 intreating human liver disease.Cellular ＆ Molecular Immunology.2004;1（1）:43-49.