Interleukin-22 (IL-22) is a recently identified T cell-derived cytokine whose biological significance remains obscure.Previously,we have shown that IL-22 plays a protective role in T cell-mediated hepatitis induced by...Interleukin-22 (IL-22) is a recently identified T cell-derived cytokine whose biological significance remains obscure.Previously,we have shown that IL-22 plays a protective role in T cell-mediated hepatitis induced by Concanavalin A (Con A),acting as a survival factor for hepatocytes.In the present paper,we demonstrate that hydrodynamic gene delivery of IL-22 cDNA driven either by a liver-specific albumin promoter or a human cytomegalovirus (CMV) promoter results in IL-22 protein expression,STAT3 activation,and expression of several anti-apoptotic proteins,including Bcl-xL,Bcl-2,and Mcl-1 in the liver.Immunohistochemical analysis reveals that IL-22 protein expression is mainly detected in the cytoplasm of hepatocytes.Overexpression of IL-22 by hydrodynamic gene delivery significantly protects against liver injury,necrosis,and apoptosis induced by administration of Con A,carbon tetrachloride (CCl_4),or the Fas agonist Jo-2 mAb.Western blot analyses show 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-22 protects against liver injury induced by a variety of toxins,suggesting the therapeutic potential of IL-22 in treating human liver disease.Cellular & Molecular Immunology.2004;1(1):43-49.展开更多
文摘Interleukin-22 (IL-22) is a recently identified T cell-derived cytokine whose biological significance remains obscure.Previously,we have shown that IL-22 plays a protective role in T cell-mediated hepatitis induced by Concanavalin A (Con A),acting as a survival factor for hepatocytes.In the present paper,we demonstrate that hydrodynamic gene delivery of IL-22 cDNA driven either by a liver-specific albumin promoter or a human cytomegalovirus (CMV) promoter results in IL-22 protein expression,STAT3 activation,and expression of several anti-apoptotic proteins,including Bcl-xL,Bcl-2,and Mcl-1 in the liver.Immunohistochemical analysis reveals that IL-22 protein expression is mainly detected in the cytoplasm of hepatocytes.Overexpression of IL-22 by hydrodynamic gene delivery significantly protects against liver injury,necrosis,and apoptosis induced by administration of Con A,carbon tetrachloride (CCl_4),or the Fas agonist Jo-2 mAb.Western blot analyses show 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-22 protects against liver injury induced by a variety of toxins,suggesting the therapeutic potential of IL-22 in treating human liver disease.Cellular & Molecular Immunology.2004;1(1):43-49.
