Pegylated interferon-α2b and ribavirin decrease claudin-1 and E-cadherin expression in HepG2 and Huh-7.5 cells

Background. Hepatitis C virus (HCV) infection usually results in long-term viremia. Entry of HCV into the he-patocyte 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...

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Main Authors: Rendón Huerta, Erika P., Torres Martínez, Ana, Charles Niño, Claudia, Rivas Estilla, Ana María, Páez, A., Fortoul, Teresa I., Montaño, Luis F.
Format: Article
Language:English
Published: 2013
Subjects:
Online Access:http://eprints.uanl.mx/23504/1/23504.pdf
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author Rendón Huerta, Erika P.
Torres Martínez, Ana
Charles Niño, Claudia
Rivas Estilla, Ana María
Páez, A.
Fortoul, Teresa I.
Montaño, Luis F.
author_facet Rendón Huerta, Erika P.
Torres Martínez, Ana
Charles Niño, Claudia
Rivas Estilla, Ana María
Páez, A.
Fortoul, Teresa I.
Montaño, Luis F.
author_sort Rendón Huerta, Erika P.
collection Repositorio Institucional
description Background. Hepatitis C virus (HCV) infection usually results in long-term viremia. Entry of HCV into the he-patocyte 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 ug 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.
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spelling eprints-235042023-05-18T18:51:34Z http://eprints.uanl.mx/23504/ Pegylated interferon-α2b and ribavirin decrease claudin-1 and E-cadherin expression in HepG2 and Huh-7.5 cells Rendón Huerta, Erika P. Torres Martínez, Ana Charles Niño, Claudia Rivas Estilla, Ana María Páez, A. Fortoul, Teresa I. Montaño, Luis F. RC Medicina Interna, Psiquiatría, Neurología Background. Hepatitis C virus (HCV) infection usually results in long-term viremia. Entry of HCV into the he-patocyte 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 ug 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. 2013 Article PeerReviewed text en cc_by_nc_nd http://eprints.uanl.mx/23504/1/23504.pdf http://eprints.uanl.mx/23504/1.haspreviewThumbnailVersion/23504.pdf Rendón Huerta, Erika P. y Torres Martínez, Ana y Charles Niño, Claudia y Rivas Estilla, Ana María y Páez, A. y Fortoul, Teresa I. y Montaño, Luis F. (2013) Pegylated interferon-α2b and ribavirin decrease claudin-1 and E-cadherin expression in HepG2 and Huh-7.5 cells. Annals of hepatology, 12 (4). pp. 448-457. ISSN 1665-2681 http://doi.org/10.1016/S1665-2681(19)31346-8 doi:10.1016/S1665-2681(19)31346-8
spellingShingle RC Medicina Interna, Psiquiatría, Neurología
Rendón Huerta, Erika P.
Torres Martínez, Ana
Charles Niño, Claudia
Rivas Estilla, Ana María
Páez, A.
Fortoul, Teresa I.
Montaño, Luis F.
Pegylated interferon-α2b and ribavirin decrease claudin-1 and E-cadherin expression in HepG2 and Huh-7.5 cells
thumbnail https://rediab.uanl.mx/themes/sandal5/images/online.png
title Pegylated interferon-α2b and ribavirin decrease claudin-1 and E-cadherin expression in HepG2 and Huh-7.5 cells
title_full Pegylated interferon-α2b and ribavirin decrease claudin-1 and E-cadherin expression in HepG2 and Huh-7.5 cells
title_fullStr Pegylated interferon-α2b and ribavirin decrease claudin-1 and E-cadherin expression in HepG2 and Huh-7.5 cells
title_full_unstemmed Pegylated interferon-α2b and ribavirin decrease claudin-1 and E-cadherin expression in HepG2 and Huh-7.5 cells
title_short Pegylated interferon-α2b and ribavirin decrease claudin-1 and E-cadherin expression in HepG2 and Huh-7.5 cells
title_sort pegylated interferon α2b and ribavirin decrease claudin 1 and e cadherin expression in hepg2 and huh 7 5 cells
topic RC Medicina Interna, Psiquiatría, Neurología
url http://eprints.uanl.mx/23504/1/23504.pdf
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