Cargando…
Metformin activates type I interferon signaling against HCV via activation of adenosine monophosphate-activated protein kinase
Activation of the type I interferon (IFN) signaling pathway is essential for the eradication of hepatitis C virus (HCV). Metformin can activate adenosine monophosphate-activated protein kinase (AMPK) to reduce insulin resistance. Cross talks between AMPK and IFN signaling remain unclear. To understa...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696152/ https://www.ncbi.nlm.nih.gov/pubmed/29190886 http://dx.doi.org/10.18632/oncotarget.20248 |
_version_ | 1783280386021785600 |
---|---|
author | Tsai, Wei-Lun Chang, Tsung-Hsien Sun, Wei-Chi Chan, Hoi-Hung Wu, Chun-Ching Hsu, Ping-I Cheng, Jin-Shiung Yu, Ming-Lung |
author_facet | Tsai, Wei-Lun Chang, Tsung-Hsien Sun, Wei-Chi Chan, Hoi-Hung Wu, Chun-Ching Hsu, Ping-I Cheng, Jin-Shiung Yu, Ming-Lung |
author_sort | Tsai, Wei-Lun |
collection | PubMed |
description | Activation of the type I interferon (IFN) signaling pathway is essential for the eradication of hepatitis C virus (HCV). Metformin can activate adenosine monophosphate-activated protein kinase (AMPK) to reduce insulin resistance. Cross talks between AMPK and IFN signaling remain unclear. To understand the influence of metformin on the type I IFN signaling pathway and HCV infection, the full-length HCV replicon OR6 cells and the infectious HCV clones JFH1 were used to assess the anti-HCV effect of the insulin sensitizers, metformin and pioglitazone. Immunofluorescence staining and the immunoblotting of HCV viral protein demonstrated that metformin, but not pioglitazone, inhibited HCV replication in OR-6 and JFH-1-infected Huh 7.5.1 cells. Immunoblotting data showed that metformin activated the phosphorylation of STAT-1 and STAT-2 in OR-6 and JFH-1 infected Huh 7.5.1 cells. Metformin enhanced the phosphorylation of AMPK, and the metformin-activated IFN signaling was down-regulated by AMPK inhibitor. After treatment of AMPK inhibitor, the level of HCV core protein decreased by metformin can be rescued. In conclusion, metformin activates type I interferon signaling and inhibits the replication of HCV via activation of AMPK. |
format | Online Article Text |
id | pubmed-5696152 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-56961522017-11-29 Metformin activates type I interferon signaling against HCV via activation of adenosine monophosphate-activated protein kinase Tsai, Wei-Lun Chang, Tsung-Hsien Sun, Wei-Chi Chan, Hoi-Hung Wu, Chun-Ching Hsu, Ping-I Cheng, Jin-Shiung Yu, Ming-Lung Oncotarget Research Paper Activation of the type I interferon (IFN) signaling pathway is essential for the eradication of hepatitis C virus (HCV). Metformin can activate adenosine monophosphate-activated protein kinase (AMPK) to reduce insulin resistance. Cross talks between AMPK and IFN signaling remain unclear. To understand the influence of metformin on the type I IFN signaling pathway and HCV infection, the full-length HCV replicon OR6 cells and the infectious HCV clones JFH1 were used to assess the anti-HCV effect of the insulin sensitizers, metformin and pioglitazone. Immunofluorescence staining and the immunoblotting of HCV viral protein demonstrated that metformin, but not pioglitazone, inhibited HCV replication in OR-6 and JFH-1-infected Huh 7.5.1 cells. Immunoblotting data showed that metformin activated the phosphorylation of STAT-1 and STAT-2 in OR-6 and JFH-1 infected Huh 7.5.1 cells. Metformin enhanced the phosphorylation of AMPK, and the metformin-activated IFN signaling was down-regulated by AMPK inhibitor. After treatment of AMPK inhibitor, the level of HCV core protein decreased by metformin can be rescued. In conclusion, metformin activates type I interferon signaling and inhibits the replication of HCV via activation of AMPK. Impact Journals LLC 2017-08-14 /pmc/articles/PMC5696152/ /pubmed/29190886 http://dx.doi.org/10.18632/oncotarget.20248 Text en Copyright: © 2017 Tsai et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Research Paper Tsai, Wei-Lun Chang, Tsung-Hsien Sun, Wei-Chi Chan, Hoi-Hung Wu, Chun-Ching Hsu, Ping-I Cheng, Jin-Shiung Yu, Ming-Lung Metformin activates type I interferon signaling against HCV via activation of adenosine monophosphate-activated protein kinase |
title | Metformin activates type I interferon signaling against HCV via activation of adenosine monophosphate-activated protein kinase |
title_full | Metformin activates type I interferon signaling against HCV via activation of adenosine monophosphate-activated protein kinase |
title_fullStr | Metformin activates type I interferon signaling against HCV via activation of adenosine monophosphate-activated protein kinase |
title_full_unstemmed | Metformin activates type I interferon signaling against HCV via activation of adenosine monophosphate-activated protein kinase |
title_short | Metformin activates type I interferon signaling against HCV via activation of adenosine monophosphate-activated protein kinase |
title_sort | metformin activates type i interferon signaling against hcv via activation of adenosine monophosphate-activated protein kinase |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696152/ https://www.ncbi.nlm.nih.gov/pubmed/29190886 http://dx.doi.org/10.18632/oncotarget.20248 |
work_keys_str_mv | AT tsaiweilun metforminactivatestypeiinterferonsignalingagainsthcvviaactivationofadenosinemonophosphateactivatedproteinkinase AT changtsunghsien metforminactivatestypeiinterferonsignalingagainsthcvviaactivationofadenosinemonophosphateactivatedproteinkinase AT sunweichi metforminactivatestypeiinterferonsignalingagainsthcvviaactivationofadenosinemonophosphateactivatedproteinkinase AT chanhoihung metforminactivatestypeiinterferonsignalingagainsthcvviaactivationofadenosinemonophosphateactivatedproteinkinase AT wuchunching metforminactivatestypeiinterferonsignalingagainsthcvviaactivationofadenosinemonophosphateactivatedproteinkinase AT hsupingi metforminactivatestypeiinterferonsignalingagainsthcvviaactivationofadenosinemonophosphateactivatedproteinkinase AT chengjinshiung metforminactivatestypeiinterferonsignalingagainsthcvviaactivationofadenosinemonophosphateactivatedproteinkinase AT yuminglung metforminactivatestypeiinterferonsignalingagainsthcvviaactivationofadenosinemonophosphateactivatedproteinkinase |