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β-sitosterol ameliorates influenza A virus-induced proinflammatory response and acute lung injury in mice by disrupting the cross-talk between RIG-I and IFN/STAT signaling

β-Sitosterol (24-ethyl-5-cholestene-3-ol) is a common phytosterol Chinese medical plants that has been shown to possess antioxidant and anti-inflammatory activity. In this study we investigated the effects of β-sitosterol on influenza virus-induced inflammation and acute lung injury and the molecula...

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Autores principales: Zhou, Bei-xian, Li, Jing, Liang, Xiao-li, Pan, Xi-ping, Hao, Yan-bing, Xie, Pei-fang, Jiang, Hai-ming, Yang, Zi-feng, Zhong, Nan-shan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Singapore 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273125/
https://www.ncbi.nlm.nih.gov/pubmed/32504068
http://dx.doi.org/10.1038/s41401-020-0403-9
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author Zhou, Bei-xian
Li, Jing
Liang, Xiao-li
Pan, Xi-ping
Hao, Yan-bing
Xie, Pei-fang
Jiang, Hai-ming
Yang, Zi-feng
Zhong, Nan-shan
author_facet Zhou, Bei-xian
Li, Jing
Liang, Xiao-li
Pan, Xi-ping
Hao, Yan-bing
Xie, Pei-fang
Jiang, Hai-ming
Yang, Zi-feng
Zhong, Nan-shan
author_sort Zhou, Bei-xian
collection PubMed
description β-Sitosterol (24-ethyl-5-cholestene-3-ol) is a common phytosterol Chinese medical plants that has been shown to possess antioxidant and anti-inflammatory activity. In this study we investigated the effects of β-sitosterol on influenza virus-induced inflammation and acute lung injury and the molecular mechanisms. We demonstrate that β-sitosterol (150–450 μg/mL) dose-dependently suppresses inflammatory response through NF-κB and p38 mitogen-activated protein kinase (MAPK) signaling in influenza A virus (IAV)-infected cells, which was accompanied by decreased induction of interferons (IFNs) (including Type I and III IFN). Furthermore, we revealed that the anti-inflammatory effect of β-sitosterol resulted from its inhibitory effect on retinoic acid-inducible gene I (RIG-I) signaling, led to decreased STAT1 signaling, thus affecting the transcriptional activity of ISGF3 (interferon-stimulated gene factor 3) complexes and resulting in abrogation of the IAV-induced proinflammatory amplification effect in IFN-sensitized cells. Moreover, β-sitosterol treatment attenuated RIG-I-mediated apoptotic injury of alveolar epithelial cells (AEC) via downregulation of pro-apoptotic factors. In a mouse model of influenza, pre-administration of β-sitosterol (50, 200 mg·kg(−1)·d(−1), i.g., for 2 days) dose-dependently ameliorated IAV-mediated recruitment of pathogenic cytotoxic T cells and immune dysregulation. In addition, pre-administration of β-sitosterol protected mice from lethal IAV infection. Our data suggest that β-sitosterol blocks the immune response mediated by RIG-I signaling and deleterious IFN production, providing a potential benefit for the treatment of influenza.
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spelling pubmed-72731252020-06-05 β-sitosterol ameliorates influenza A virus-induced proinflammatory response and acute lung injury in mice by disrupting the cross-talk between RIG-I and IFN/STAT signaling Zhou, Bei-xian Li, Jing Liang, Xiao-li Pan, Xi-ping Hao, Yan-bing Xie, Pei-fang Jiang, Hai-ming Yang, Zi-feng Zhong, Nan-shan Acta Pharmacol Sin Article β-Sitosterol (24-ethyl-5-cholestene-3-ol) is a common phytosterol Chinese medical plants that has been shown to possess antioxidant and anti-inflammatory activity. In this study we investigated the effects of β-sitosterol on influenza virus-induced inflammation and acute lung injury and the molecular mechanisms. We demonstrate that β-sitosterol (150–450 μg/mL) dose-dependently suppresses inflammatory response through NF-κB and p38 mitogen-activated protein kinase (MAPK) signaling in influenza A virus (IAV)-infected cells, which was accompanied by decreased induction of interferons (IFNs) (including Type I and III IFN). Furthermore, we revealed that the anti-inflammatory effect of β-sitosterol resulted from its inhibitory effect on retinoic acid-inducible gene I (RIG-I) signaling, led to decreased STAT1 signaling, thus affecting the transcriptional activity of ISGF3 (interferon-stimulated gene factor 3) complexes and resulting in abrogation of the IAV-induced proinflammatory amplification effect in IFN-sensitized cells. Moreover, β-sitosterol treatment attenuated RIG-I-mediated apoptotic injury of alveolar epithelial cells (AEC) via downregulation of pro-apoptotic factors. In a mouse model of influenza, pre-administration of β-sitosterol (50, 200 mg·kg(−1)·d(−1), i.g., for 2 days) dose-dependently ameliorated IAV-mediated recruitment of pathogenic cytotoxic T cells and immune dysregulation. In addition, pre-administration of β-sitosterol protected mice from lethal IAV infection. Our data suggest that β-sitosterol blocks the immune response mediated by RIG-I signaling and deleterious IFN production, providing a potential benefit for the treatment of influenza. Springer Singapore 2020-06-05 2020-09 /pmc/articles/PMC7273125/ /pubmed/32504068 http://dx.doi.org/10.1038/s41401-020-0403-9 Text en © CPS and SIMM 2020
spellingShingle Article
Zhou, Bei-xian
Li, Jing
Liang, Xiao-li
Pan, Xi-ping
Hao, Yan-bing
Xie, Pei-fang
Jiang, Hai-ming
Yang, Zi-feng
Zhong, Nan-shan
β-sitosterol ameliorates influenza A virus-induced proinflammatory response and acute lung injury in mice by disrupting the cross-talk between RIG-I and IFN/STAT signaling
title β-sitosterol ameliorates influenza A virus-induced proinflammatory response and acute lung injury in mice by disrupting the cross-talk between RIG-I and IFN/STAT signaling
title_full β-sitosterol ameliorates influenza A virus-induced proinflammatory response and acute lung injury in mice by disrupting the cross-talk between RIG-I and IFN/STAT signaling
title_fullStr β-sitosterol ameliorates influenza A virus-induced proinflammatory response and acute lung injury in mice by disrupting the cross-talk between RIG-I and IFN/STAT signaling
title_full_unstemmed β-sitosterol ameliorates influenza A virus-induced proinflammatory response and acute lung injury in mice by disrupting the cross-talk between RIG-I and IFN/STAT signaling
title_short β-sitosterol ameliorates influenza A virus-induced proinflammatory response and acute lung injury in mice by disrupting the cross-talk between RIG-I and IFN/STAT signaling
title_sort β-sitosterol ameliorates influenza a virus-induced proinflammatory response and acute lung injury in mice by disrupting the cross-talk between rig-i and ifn/stat signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273125/
https://www.ncbi.nlm.nih.gov/pubmed/32504068
http://dx.doi.org/10.1038/s41401-020-0403-9
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