Resumen

Background: Hepatitis C virus (HCV) infection usually results in long-term viremia. Entry of HCV into the hepatocyte requires claudin-1, -6, -9 and occludin. The efficacy of Pegylated interferon-á(PEG-IFN) treatment against HCV infection increased when ribavirin (RBV) was added to the therapeutic scheme. Our aim was to investigate if PEG-IFN plus RBV regulate claudin expression. Material and methods: HepG2, Huh-7 and Huh-7.5 cells were treated with PEG-IFN-á2a or á2b and/or RBV at different times before obtaining the cytosolic, membrane and cytoskeletal fractions. Claudin-1, 3, 4, 6, and 9, E-cadherin and occludin expression was evaluated by Western blot analysis. Transepithelial electrical resistance (TER) was also determined. Results: Claudin-1, 3, 4, 6, E-cadherin and occludin are constitutively expressed mainly in HepG2 cell membrane. Claudin-1 and E-cadherin cell membrane expression diminished after exposure to PEGIFNá2b (50 ng) + RBV(50 ìg); the maximal decrease was observed with 200 ng of PEG-IFNá2b + 200 ìg of RBV. The effect was less intense with PEG-IFNá2a. The inhibition of claudin-1 and E-cadherin expression in Huh-7 and Huh-7.5 cells was only observed with 200 ng of PEG-IFNá2b + 200 ìg of RBV. TER diminished marginally in the HCV containing hepatoma cells with 200 ng of PEG-IFNá2b + 200 ìg of RBV. Claudin-1 mRNA expression level was not affected by the combined treatment. Conclusion: The increased therapeutic efficacy of the PEG-IFNá2b plus RBV treatment could be secondary to the inhibition of claudin-1 and E-cadherin cell membrane expression.

Palabras clave: Tight junction proteins hepatitis C virus claudins.

2013-07-15   |   650 visitas   |   Evalua este artículo 0 valoraciones

Vol. 12 Núm.4. Julio-Agosto 2013 Pags. 616-625 Ann Hepatol 2013; 12(4)