Pegylated interferon-α2b and ribavirin decrease claudin-1 and E-cadherin expression in HepG2 and Huh-7.5 cells
Journal Title: Annals of Hepatology - Year 2013, Vol 12, Issue 4
Abstract
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-α (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-α2a or α2b 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 PEGIFNα2b (50 ng) + RBV(50 μg); the maximal decrease was observed with 200 ng of PEG-IFNα2b + 200 μg of RBV. The effect was less intense with PEG-IFNα2a. 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-IFNα2b + 200 μg of RBV. TER diminished marginally in the HCV containing hepatoma cells with 200 ng of PEG-IFNα2b + 200 μg of RBV. Claudin-1 mRNA expression level was not affected by the combined treatment. Conclusion. The increased therapeutic efficacy of the PEG-IFNα2b plus RBV treatment could be secondary to the inhibition of claudin-1 and E-cadherin cell membrane expression.
Authors and Affiliations
Erika P. Rendón-Huerta, Ana Torres-Martínez, Claudia Charles-Niño, Ana M. Rivas-Estilla, A. Paez, Teresa I. Fortoul, Luis F. Montaño
Dress syndrome and fulminant hepatic failure induced by lamotrigine
Lamotrigine is a non-aromatic antiepileptic drug. Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a severe idiosyncratic reaction to drugs, especially anti-epileptic drugs. Associated clinical featu...
Conversion to mycophenolate mofetil monotherapy in liver recipients: Calcineurin inhibitor levels are key
The use of calcineurin inhibitors (CNI) after liver transplantation is associated with post-transplant nephrotoxicity. Conversion to mycophenolate mofetil (MMF) monotherapy improves renal function, but is related to gra...
A New Stage in Annals of Hepatology
-<br/><br/>
Intrahepatic, perihilar and distal cholangiocarcinoma: Management and outcomes
Introduction and aims. Cholangiocarcinomas are a heterogeneous group of tumors that can be classified into three clinically distinct types of cancers, intrahepatic, perihilar and distal cholangiocarcinoma. The inconsist...
Acute phase proteins for the diagnosis of bacterial infection and prediction of mortality in acute complications of cirrhosis
Introduction. Bacterial infection is a frequent complication in patients with decompensated liver cirrhosis and is related to high mortality rates during follow-up of these individuals. We sought to evaluate the diagnost...