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Chrysophanol Exerts Anti-inflammatory Activity by Targeting Histone Deacetylase 3 Through the High Mobility Group Protein 1-Nuclear Transcription Factor-Kappa B Signaling Pathway in vivo and in vitro

Chrysophanol (Chr) is the main monomer isolated from Rheum rhabarbarum. This study aimed to identify the potential in vitro and in vivo cytoprotective effects of Chr on lipopolysaccharide (LPS)-triggered acute lung injury (ALI). We used an ALI-murine model and constructed an inflammatory macrophage...

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Autores principales: Wen, Quan, Lau, Ngaikeung, Weng, Huandi, Ye, Peng, Du, Shaohui, Li, Chun, Lv, Jianping, Li, Hui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868569/
https://www.ncbi.nlm.nih.gov/pubmed/33569375
http://dx.doi.org/10.3389/fbioe.2020.623866
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author Wen, Quan
Lau, Ngaikeung
Weng, Huandi
Ye, Peng
Du, Shaohui
Li, Chun
Lv, Jianping
Li, Hui
author_facet Wen, Quan
Lau, Ngaikeung
Weng, Huandi
Ye, Peng
Du, Shaohui
Li, Chun
Lv, Jianping
Li, Hui
author_sort Wen, Quan
collection PubMed
description Chrysophanol (Chr) is the main monomer isolated from Rheum rhabarbarum. This study aimed to identify the potential in vitro and in vivo cytoprotective effects of Chr on lipopolysaccharide (LPS)-triggered acute lung injury (ALI). We used an ALI-murine model and constructed an inflammatory macrophage in vitro cell model to determine the cellular mechanisms involved in Chr-mediated activity. To observe the vital role of histone deacetylase 3 (HDAC3) in abolishing inflammation action, HDAC3 was downregulated using small interfering RNA. Analysis of the expression of nuclear transcription factor-kappa B p65 (NF-κB p65) and molecules of its downstream signaling pathway were assessed in vitro and in lung tissue samples using the mouse model. Concentrations of tumor necrosis factor-α, interleukin-1β, high mobility group protein 1 (HMGB1), and interleukin-16 in supernatants and the bronchoalveolar lavage fluid were measured using enzyme-linked immunosorbent assay. A reporter gene assay measured HMGB1 activity, and NF-κB p65 and HMGB1 intracellular localization was determined by immunofluorescence detection on histological lung samples from Chr-treated mice. The protein interactions between HMGB1, HDAC3, and NF-κB p65 were tested by co-immunoprecipitation. Chr treatment relieved LPS-induced lung lesions. Chr also enhanced superoxide dismutase levels in ALI mice. Chr reduced the LPS-induced protein expression of NF-κB and its related pathway molecules in both in vivo and in vitro models. Moreover, Chr downregulated LPS-enhanced HMGB1 expression, acetylation, and nuclear nucleocytoplasmic translocation. However, HDAC3 knockdown substantially reduced Chr-mediated HDAC3/NF-κB expression. Furthermore, Chr enhanced HMGB1/HDAC3/NF-κB p65 complex interaction, whereas HDAC3 knockdown reduced Chr-mediated HMGB1/HDAC3/NF-κB p65 formation. This study showed that the protective effects induced by Chr were associated with the regulation of the HMGB1/NF-κB pathway via HDAC3.
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spelling pubmed-78685692021-02-09 Chrysophanol Exerts Anti-inflammatory Activity by Targeting Histone Deacetylase 3 Through the High Mobility Group Protein 1-Nuclear Transcription Factor-Kappa B Signaling Pathway in vivo and in vitro Wen, Quan Lau, Ngaikeung Weng, Huandi Ye, Peng Du, Shaohui Li, Chun Lv, Jianping Li, Hui Front Bioeng Biotechnol Bioengineering and Biotechnology Chrysophanol (Chr) is the main monomer isolated from Rheum rhabarbarum. This study aimed to identify the potential in vitro and in vivo cytoprotective effects of Chr on lipopolysaccharide (LPS)-triggered acute lung injury (ALI). We used an ALI-murine model and constructed an inflammatory macrophage in vitro cell model to determine the cellular mechanisms involved in Chr-mediated activity. To observe the vital role of histone deacetylase 3 (HDAC3) in abolishing inflammation action, HDAC3 was downregulated using small interfering RNA. Analysis of the expression of nuclear transcription factor-kappa B p65 (NF-κB p65) and molecules of its downstream signaling pathway were assessed in vitro and in lung tissue samples using the mouse model. Concentrations of tumor necrosis factor-α, interleukin-1β, high mobility group protein 1 (HMGB1), and interleukin-16 in supernatants and the bronchoalveolar lavage fluid were measured using enzyme-linked immunosorbent assay. A reporter gene assay measured HMGB1 activity, and NF-κB p65 and HMGB1 intracellular localization was determined by immunofluorescence detection on histological lung samples from Chr-treated mice. The protein interactions between HMGB1, HDAC3, and NF-κB p65 were tested by co-immunoprecipitation. Chr treatment relieved LPS-induced lung lesions. Chr also enhanced superoxide dismutase levels in ALI mice. Chr reduced the LPS-induced protein expression of NF-κB and its related pathway molecules in both in vivo and in vitro models. Moreover, Chr downregulated LPS-enhanced HMGB1 expression, acetylation, and nuclear nucleocytoplasmic translocation. However, HDAC3 knockdown substantially reduced Chr-mediated HDAC3/NF-κB expression. Furthermore, Chr enhanced HMGB1/HDAC3/NF-κB p65 complex interaction, whereas HDAC3 knockdown reduced Chr-mediated HMGB1/HDAC3/NF-κB p65 formation. This study showed that the protective effects induced by Chr were associated with the regulation of the HMGB1/NF-κB pathway via HDAC3. Frontiers Media S.A. 2021-01-25 /pmc/articles/PMC7868569/ /pubmed/33569375 http://dx.doi.org/10.3389/fbioe.2020.623866 Text en Copyright © 2021 Wen, Lau, Weng, Ye, Du, Li, Lv and Li. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Bioengineering and Biotechnology
Wen, Quan
Lau, Ngaikeung
Weng, Huandi
Ye, Peng
Du, Shaohui
Li, Chun
Lv, Jianping
Li, Hui
Chrysophanol Exerts Anti-inflammatory Activity by Targeting Histone Deacetylase 3 Through the High Mobility Group Protein 1-Nuclear Transcription Factor-Kappa B Signaling Pathway in vivo and in vitro
title Chrysophanol Exerts Anti-inflammatory Activity by Targeting Histone Deacetylase 3 Through the High Mobility Group Protein 1-Nuclear Transcription Factor-Kappa B Signaling Pathway in vivo and in vitro
title_full Chrysophanol Exerts Anti-inflammatory Activity by Targeting Histone Deacetylase 3 Through the High Mobility Group Protein 1-Nuclear Transcription Factor-Kappa B Signaling Pathway in vivo and in vitro
title_fullStr Chrysophanol Exerts Anti-inflammatory Activity by Targeting Histone Deacetylase 3 Through the High Mobility Group Protein 1-Nuclear Transcription Factor-Kappa B Signaling Pathway in vivo and in vitro
title_full_unstemmed Chrysophanol Exerts Anti-inflammatory Activity by Targeting Histone Deacetylase 3 Through the High Mobility Group Protein 1-Nuclear Transcription Factor-Kappa B Signaling Pathway in vivo and in vitro
title_short Chrysophanol Exerts Anti-inflammatory Activity by Targeting Histone Deacetylase 3 Through the High Mobility Group Protein 1-Nuclear Transcription Factor-Kappa B Signaling Pathway in vivo and in vitro
title_sort chrysophanol exerts anti-inflammatory activity by targeting histone deacetylase 3 through the high mobility group protein 1-nuclear transcription factor-kappa b signaling pathway in vivo and in vitro
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868569/
https://www.ncbi.nlm.nih.gov/pubmed/33569375
http://dx.doi.org/10.3389/fbioe.2020.623866
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