目的通过膀胱灌注N蛳甲基亚硝基脲(M N U)诱导近交系大鼠膀胱肿瘤。方法选取F344大鼠20只,膀胱灌注M N U,每2周1次,共5次;于第14周处死动物,取膀胱肿瘤组织测M H C蛳I及病理观察。结果M N U组肿瘤发生率为100%;膀胱肿瘤的M H C蛳I表达较...目的通过膀胱灌注N蛳甲基亚硝基脲(M N U)诱导近交系大鼠膀胱肿瘤。方法选取F344大鼠20只,膀胱灌注M N U,每2周1次,共5次;于第14周处死动物,取膀胱肿瘤组织测M H C蛳I及病理观察。结果M N U组肿瘤发生率为100%;膀胱肿瘤的M H C蛳I表达较高(58.60%￣93.80%)。结论M N U可成功诱导F344大鼠膀胱肿瘤的形成,是肿瘤免疫治疗的理想模型。展开更多
Alcoholic patients have a high incidence of hepatitis C virus （HCV） infection. Alcohol consumption enhances the severity of the HCV disease course and worsens the outcome of chronic hepatitis C. The accumulation of ...Alcoholic patients have a high incidence of hepatitis C virus （HCV） infection. Alcohol consumption enhances the severity of the HCV disease course and worsens the outcome of chronic hepatitis C. The accumulation of virally infected cells in the liver is related to the HCV- induced inability of the immune system to recognize infected cells and to develop the immune responses. This review covers the effects of HCV proteins and ethanol on major histocompatibility complex （MHC） class Ⅰ- and class Ⅱ-restricted antigen presentation. Here, we discuss the liver which functions as an immune privilege organ; factors, which affect cleavage and loading of antigenic peptides onto MHC class I and class ~I in hepatocytes and dendritic cells, and the modulating effects of ethanol and HCV on antigen presentation by liver cells. Altered antigen presentation in the liver limits the ability ＇of the immune system to clear HCV and infected cells and contributes to disease progression. HCV by itself affects dendritic cell function, switching their cytokine profile to the suppressive phenotype of interleukin-10 （IL-10） and transforming growth factor beta （TGFβ） predominance, preventing cell maturation and allostimulation capacity. The synergistic action of ethanol with HCV results in the suppression of MHC class Ⅱ-restricted antigen presentation. In addition, ethanol metabolism and HCV proteins reduce proteasome function and interferon signaling, thereby suppressing the generation of peptides for MHC class I -restricted antigen presentation. Collectively, ethanol exposure further impairs antigen presentation in HCV-infected liver cells, which may provide a partial explanation for exacerbations and the poor outcome of HCV infection in alcoholics.展开更多
文摘目的通过膀胱灌注N蛳甲基亚硝基脲(M N U)诱导近交系大鼠膀胱肿瘤。方法选取F344大鼠20只,膀胱灌注M N U,每2周1次,共5次;于第14周处死动物,取膀胱肿瘤组织测M H C蛳I及病理观察。结果M N U组肿瘤发生率为100%;膀胱肿瘤的M H C蛳I表达较高(58.60%￣93.80%)。结论M N U可成功诱导F344大鼠膀胱肿瘤的形成,是肿瘤免疫治疗的理想模型。
基金Supported by Development funds from Section of Gastroenterology/Hepatology, Internal Medicine, University of Nebraska Medical Center
文摘Alcoholic patients have a high incidence of hepatitis C virus （HCV） infection. Alcohol consumption enhances the severity of the HCV disease course and worsens the outcome of chronic hepatitis C. The accumulation of virally infected cells in the liver is related to the HCV- induced inability of the immune system to recognize infected cells and to develop the immune responses. This review covers the effects of HCV proteins and ethanol on major histocompatibility complex （MHC） class Ⅰ- and class Ⅱ-restricted antigen presentation. Here, we discuss the liver which functions as an immune privilege organ; factors, which affect cleavage and loading of antigenic peptides onto MHC class I and class ~I in hepatocytes and dendritic cells, and the modulating effects of ethanol and HCV on antigen presentation by liver cells. Altered antigen presentation in the liver limits the ability ＇of the immune system to clear HCV and infected cells and contributes to disease progression. HCV by itself affects dendritic cell function, switching their cytokine profile to the suppressive phenotype of interleukin-10 （IL-10） and transforming growth factor beta （TGFβ） predominance, preventing cell maturation and allostimulation capacity. The synergistic action of ethanol with HCV results in the suppression of MHC class Ⅱ-restricted antigen presentation. In addition, ethanol metabolism and HCV proteins reduce proteasome function and interferon signaling, thereby suppressing the generation of peptides for MHC class I -restricted antigen presentation. Collectively, ethanol exposure further impairs antigen presentation in HCV-infected liver cells, which may provide a partial explanation for exacerbations and the poor outcome of HCV infection in alcoholics.
