TY - JOUR
T1 - HCV inhibits antigen processing and presentation and induces oxidative stress response in gastric mucosa
AU - De Re, Valli
AU - Simula, Maria Paola
AU - Cannizzaro, Renato
AU - Sansonno, Domenico
AU - Canzonieri, Vincenzo
AU - Gloghini, Annunziata
AU - Carbone, Antonino
AU - Colombatti, Alfonso
AU - Marin, Maria Dolores
AU - De Zorzi, Mariangela
AU - Toffoli, Giuseppe
PY - 2008/9
Y1 - 2008/9
N2 - Productive hepatitis C virus (HCV) infection appears to be primarily confined to the liver. However, a wide variety of extrahepatic disease manifestations are associated with the infection and HCV RNA has been frequently detected in gastric mucosa. The present study aims to determine molecular alterations present in vivo in the stomach where HCV expression does not induce a carcinoma but a lymphoma, thus extending the knowledge of alterations in intracellular pathways consequent to HCV infection. We compared, by 2-D DIGE, the gastric protein expression profile from six HCV positive and six HCV negative samples lacking neoplastic or dysplastic conditions. In HCV positive tissue we observed a down regulation of proteins involved in MHC maturation and assembly, antigen processing and presentation and ER stress, in addition to an up regulation of proteins involved in cellular oxidative stress responses. Ubiquinol-cytochrome-C-reductase (UQCRFS1), part of the mitochondrial respiratory chain complex-III, was identified as the most up regulated protein. Data were confirmed by Western blot and immunohistochemistry. Our results demonstrate a HCV negative influence on the different pathways that determine antigen processing and presentation via MHC-I and the cellular attempts to counteract HCV induced oxidative stress. Both these processes facilitate immune escape and cell survival and probably contribute to HCV chronicization.
AB - Productive hepatitis C virus (HCV) infection appears to be primarily confined to the liver. However, a wide variety of extrahepatic disease manifestations are associated with the infection and HCV RNA has been frequently detected in gastric mucosa. The present study aims to determine molecular alterations present in vivo in the stomach where HCV expression does not induce a carcinoma but a lymphoma, thus extending the knowledge of alterations in intracellular pathways consequent to HCV infection. We compared, by 2-D DIGE, the gastric protein expression profile from six HCV positive and six HCV negative samples lacking neoplastic or dysplastic conditions. In HCV positive tissue we observed a down regulation of proteins involved in MHC maturation and assembly, antigen processing and presentation and ER stress, in addition to an up regulation of proteins involved in cellular oxidative stress responses. Ubiquinol-cytochrome-C-reductase (UQCRFS1), part of the mitochondrial respiratory chain complex-III, was identified as the most up regulated protein. Data were confirmed by Western blot and immunohistochemistry. Our results demonstrate a HCV negative influence on the different pathways that determine antigen processing and presentation via MHC-I and the cellular attempts to counteract HCV induced oxidative stress. Both these processes facilitate immune escape and cell survival and probably contribute to HCV chronicization.
KW - Cancer
KW - Hepatitis C virus
KW - Inflammation
KW - Proteomic
KW - Ubiquinol-cytochrome-C-reductase
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U2 - 10.1002/prca.200800059
DO - 10.1002/prca.200800059
M3 - Article
C2 - 21136923
AN - SCOPUS:53549122224
VL - 2
SP - 1290
EP - 1299
JO - Proteomics - Clinical Applications
JF - Proteomics - Clinical Applications
SN - 1862-8346
IS - 9
ER -