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Type I IFN induced IL1-Ra expression in hepatocytes is mediated by activating STAT6 through the formation of STAT2: STAT6 heterodimer

The biological activities of type I interferons (IFNs) are mediated by their binding to a heterodimer receptor complex (IFNAR1 and IFNAR2), resulting in the activation of the JAK (JAK1 and TYK2)-STAT (1, 2, 3, 5 isotypes) signalling pathway. Although several studies have indicated that IFN-α and IFN...

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Autores principales: Wan, Lei, Lin, Cheng-Wen, Lin, Ying-Ju, Sheu, Jim JC, Chen, Bing-Hung, Liao, Chiu-Chu, Tsai, Yuhsin, Lin, Wei-Yong, Lai, Chih-Ho, Tsai, Fuu Jen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4401122/
https://www.ncbi.nlm.nih.gov/pubmed/18494930
http://dx.doi.org/10.1111/j.1582-4934.2008.00143.x
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author Wan, Lei
Lin, Cheng-Wen
Lin, Ying-Ju
Sheu, Jim JC
Chen, Bing-Hung
Liao, Chiu-Chu
Tsai, Yuhsin
Lin, Wei-Yong
Lai, Chih-Ho
Tsai, Fuu Jen
author_facet Wan, Lei
Lin, Cheng-Wen
Lin, Ying-Ju
Sheu, Jim JC
Chen, Bing-Hung
Liao, Chiu-Chu
Tsai, Yuhsin
Lin, Wei-Yong
Lai, Chih-Ho
Tsai, Fuu Jen
author_sort Wan, Lei
collection PubMed
description The biological activities of type I interferons (IFNs) are mediated by their binding to a heterodimer receptor complex (IFNAR1 and IFNAR2), resulting in the activation of the JAK (JAK1 and TYK2)-STAT (1, 2, 3, 5 isotypes) signalling pathway. Although several studies have indicated that IFN-α and IFN-β can activate complexes containing STAT6, the biological role of this activation is still unknown. We found that exposure of hepatoma cells (HuH7 and Hep3B) to IFN-α or IFN-β led to the activation of STAT6. Activated STAT6 in turn induced the formation of STAT2: STAT6 complexes, which led to the secretion of IL-1Ra. The activation of STAT6 by type I IFN in hepatocytes was mediated by JAK1 and Tyk2. In addition, IFN-α or IFN-β significantly enhanced the stimulatory effect of IL-1β on production of IL-1Ra. The present study suggests a novel function of IFN-α and IFN-β signalling in human hepatocytes. Our results provide evidence for the mechanism how IFN-α and IFN-β modulate inflammatory responses through activation of STAT6 and production of secreted IL-1Ra.
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spelling pubmed-44011222015-04-27 Type I IFN induced IL1-Ra expression in hepatocytes is mediated by activating STAT6 through the formation of STAT2: STAT6 heterodimer Wan, Lei Lin, Cheng-Wen Lin, Ying-Ju Sheu, Jim JC Chen, Bing-Hung Liao, Chiu-Chu Tsai, Yuhsin Lin, Wei-Yong Lai, Chih-Ho Tsai, Fuu Jen J Cell Mol Med Articles The biological activities of type I interferons (IFNs) are mediated by their binding to a heterodimer receptor complex (IFNAR1 and IFNAR2), resulting in the activation of the JAK (JAK1 and TYK2)-STAT (1, 2, 3, 5 isotypes) signalling pathway. Although several studies have indicated that IFN-α and IFN-β can activate complexes containing STAT6, the biological role of this activation is still unknown. We found that exposure of hepatoma cells (HuH7 and Hep3B) to IFN-α or IFN-β led to the activation of STAT6. Activated STAT6 in turn induced the formation of STAT2: STAT6 complexes, which led to the secretion of IL-1Ra. The activation of STAT6 by type I IFN in hepatocytes was mediated by JAK1 and Tyk2. In addition, IFN-α or IFN-β significantly enhanced the stimulatory effect of IL-1β on production of IL-1Ra. The present study suggests a novel function of IFN-α and IFN-β signalling in human hepatocytes. Our results provide evidence for the mechanism how IFN-α and IFN-β modulate inflammatory responses through activation of STAT6 and production of secreted IL-1Ra. Blackwell Publishing Ltd 2008-06 2008-05-21 /pmc/articles/PMC4401122/ /pubmed/18494930 http://dx.doi.org/10.1111/j.1582-4934.2008.00143.x Text en © 2008 The Authors Journal compilation © 2008 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
spellingShingle Articles
Wan, Lei
Lin, Cheng-Wen
Lin, Ying-Ju
Sheu, Jim JC
Chen, Bing-Hung
Liao, Chiu-Chu
Tsai, Yuhsin
Lin, Wei-Yong
Lai, Chih-Ho
Tsai, Fuu Jen
Type I IFN induced IL1-Ra expression in hepatocytes is mediated by activating STAT6 through the formation of STAT2: STAT6 heterodimer
title Type I IFN induced IL1-Ra expression in hepatocytes is mediated by activating STAT6 through the formation of STAT2: STAT6 heterodimer
title_full Type I IFN induced IL1-Ra expression in hepatocytes is mediated by activating STAT6 through the formation of STAT2: STAT6 heterodimer
title_fullStr Type I IFN induced IL1-Ra expression in hepatocytes is mediated by activating STAT6 through the formation of STAT2: STAT6 heterodimer
title_full_unstemmed Type I IFN induced IL1-Ra expression in hepatocytes is mediated by activating STAT6 through the formation of STAT2: STAT6 heterodimer
title_short Type I IFN induced IL1-Ra expression in hepatocytes is mediated by activating STAT6 through the formation of STAT2: STAT6 heterodimer
title_sort type i ifn induced il1-ra expression in hepatocytes is mediated by activating stat6 through the formation of stat2: stat6 heterodimer
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4401122/
https://www.ncbi.nlm.nih.gov/pubmed/18494930
http://dx.doi.org/10.1111/j.1582-4934.2008.00143.x
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