Impairment of liver regeneration correlates with activated hepatic NKT cells in HBV transgenic mice. Export

@article{citeulike:3466561, abstract = {A fraction of HBV carriers have a risk to develop liver cancer. Because liver possesses a strong regeneration capability, surgical resection of cancerous liver or transplantation with healthy liver is an alternate choice for HBV-caused hepatocarcinoma therapy. How HBV infection affects the regeneration of hepatectomized or transplanted liver remains elusive. We report that partial hepatectomy (PHx)-induced liver regeneration was reduced in HBV transgenic (HBV-tg) mice, a model of human HBV infection. PHx markedly triggered natural killer T (NKT) cell accumulation in the hepatectomized livers of HBV-tg mice, simultaneously with enhanced interferon gamma (IFN-gamma) production and CD69 expression on hepatic NKT cells at the early stage of liver regeneration. The impairment of liver regeneration in HBV-tg mice was largely ameliorated by NKT cell depletion, but not by natural killer (NK) cell depletion. Blockage of CD1d-NKT cell interaction considerably alleviated NKT cell activation and their inhibitory effect on regenerating hepatocytes. Neutralization of IFN-gamma enhanced bromodeoxyuridine incorporation in HBV-tg mice after PHx, and IFN-gamma mainly induced hepatocyte cell cycle arrest. Adoptive transfer of NKT cells from regenerating HBV-tg liver, but not from normal mice, could inhibit liver regeneration in recipient mice. CONCLUSION: Activated NKT cells negatively regulate liver regeneration of HBV-tg mice in the PHx model.}, author = {Dong, Z. and Zhang, J. and Sun, R. and Wei, H. and Tian, Z.}, citeulike-article-id = {3466561}, citeulike-linkout-0 = {http://dx.doi.org/10.1002/hep.21597}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/17523147}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=17523147}, doi = {10.1002/hep.21597}, issn = {0270-9139}, journal = {Hepatology (Baltimore, Md.)}, keywords = {experimental, hbv, liver, nkt\_cell}, month = {June}, number = {6}, pages = {1400--1412}, posted-at = {2008-10-30 19:32:53}, priority = {2}, title = {Impairment of liver regeneration correlates with activated hepatic NKT cells in HBV transgenic mice.}, url = {http://dx.doi.org/10.1002/hep.21597}, volume = {45}, year = {2007} }

TY - JOUR ID - citeulike:3466561 L3 - citeulike-article-id:3466561 N2 - A fraction of HBV carriers have a risk to develop liver cancer. Because liver possesses a strong regeneration capability, surgical resection of cancerous liver or transplantation with healthy liver is an alternate choice for HBV-caused hepatocarcinoma therapy. How HBV infection affects the regeneration of hepatectomized or transplanted liver remains elusive. We report that partial hepatectomy (PHx)-induced liver regeneration was reduced in HBV transgenic (HBV-tg) mice, a model of human HBV infection. PHx markedly triggered natural killer T (NKT) cell accumulation in the hepatectomized livers of HBV-tg mice, simultaneously with enhanced interferon gamma (IFN-gamma) production and CD69 expression on hepatic NKT cells at the early stage of liver regeneration. The impairment of liver regeneration in HBV-tg mice was largely ameliorated by NKT cell depletion, but not by natural killer (NK) cell depletion. Blockage of CD1d-NKT cell interaction considerably alleviated NKT cell activation and their inhibitory effect on regenerating hepatocytes. Neutralization of IFN-gamma enhanced bromodeoxyuridine incorporation in HBV-tg mice after PHx, and IFN-gamma mainly induced hepatocyte cell cycle arrest. Adoptive transfer of NKT cells from regenerating HBV-tg liver, but not from normal mice, could inhibit liver regeneration in recipient mice. CONCLUSION: Activated NKT cells negatively regulate liver regeneration of HBV-tg mice in the PHx model. IS - 6 JF - Hepatology (Baltimore, Md.) SN - 0270-9139 EP - 1412 TI - Impairment of liver regeneration correlates with activated hepatic NKT cells in HBV transgenic mice. VL - 45 SP - 1400 KW - experimental KW - hbv KW - liver KW - nkt_cell AU - Dong, Z AU - Zhang, J AU - Sun, R AU - Wei, H AU - Tian, Z PY - 2007/06// UR - http://dx.doi.org/10.1002/hep.21597 ER -