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Degradation of histone deacetylase 4 via the TLR4/JAK/STAT1 signaling pathway promotes the acetylation of high mobility group box 1 (HMGB1) in lipopolysaccharide‐activated macrophages

High mobility group box 1 (HMGB1) has been proposed as crucial in the pathogenesis of many diseases including sepsis. Acetylation of HMGB1 prevents its entry into the nucleus and leads to its secretion from the cell where it can trigger inflammation. We hypothesized that histone deacetylase 4 (HDAC4...

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Autores principales: Park, Eun J., Kim, Young M., Kim, Hye J., Chang, Ki C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6026695/
https://www.ncbi.nlm.nih.gov/pubmed/29988587
http://dx.doi.org/10.1002/2211-5463.12456
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author Park, Eun J.
Kim, Young M.
Kim, Hye J.
Chang, Ki C.
author_facet Park, Eun J.
Kim, Young M.
Kim, Hye J.
Chang, Ki C.
author_sort Park, Eun J.
collection PubMed
description High mobility group box 1 (HMGB1) has been proposed as crucial in the pathogenesis of many diseases including sepsis. Acetylation of HMGB1 prevents its entry into the nucleus and leads to its secretion from the cell where it can trigger inflammation. We hypothesized that histone deacetylase 4 (HDAC4) controls the acetylation of HMGB1 in lipopolysaccharide (LPS)‐stimulated RAW264.7 cells via the janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. The results showed that LPS treatment promoted the degradation of HDAC4 in a proteasome‐dependent manner, which led to HMGB1 acetylation. In LPS‐activated RAW264.7 cells, treatment with TAK‐242 (a toll like receptor 4 inhibitor) and pyridone 6 (a JAK inhibitor) significantly inhibited HDAC4 degradation and acetylation of HMGB1, and thus prevented secretion of HMGB1. Decreased phosphorylation of STAT1 was also observed. Interestingly, HDAC4 overexpression significantly prevented the acetylation and secretion of HMGB1 in both RAW264.7 cells and isolated murine peritoneal macrophages. We conclude that HDAC4 might be a useful target for the treatment of sepsis.
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spelling pubmed-60266952018-07-09 Degradation of histone deacetylase 4 via the TLR4/JAK/STAT1 signaling pathway promotes the acetylation of high mobility group box 1 (HMGB1) in lipopolysaccharide‐activated macrophages Park, Eun J. Kim, Young M. Kim, Hye J. Chang, Ki C. FEBS Open Bio Research Articles High mobility group box 1 (HMGB1) has been proposed as crucial in the pathogenesis of many diseases including sepsis. Acetylation of HMGB1 prevents its entry into the nucleus and leads to its secretion from the cell where it can trigger inflammation. We hypothesized that histone deacetylase 4 (HDAC4) controls the acetylation of HMGB1 in lipopolysaccharide (LPS)‐stimulated RAW264.7 cells via the janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. The results showed that LPS treatment promoted the degradation of HDAC4 in a proteasome‐dependent manner, which led to HMGB1 acetylation. In LPS‐activated RAW264.7 cells, treatment with TAK‐242 (a toll like receptor 4 inhibitor) and pyridone 6 (a JAK inhibitor) significantly inhibited HDAC4 degradation and acetylation of HMGB1, and thus prevented secretion of HMGB1. Decreased phosphorylation of STAT1 was also observed. Interestingly, HDAC4 overexpression significantly prevented the acetylation and secretion of HMGB1 in both RAW264.7 cells and isolated murine peritoneal macrophages. We conclude that HDAC4 might be a useful target for the treatment of sepsis. John Wiley and Sons Inc. 2018-06-05 /pmc/articles/PMC6026695/ /pubmed/29988587 http://dx.doi.org/10.1002/2211-5463.12456 Text en © 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Park, Eun J.
Kim, Young M.
Kim, Hye J.
Chang, Ki C.
Degradation of histone deacetylase 4 via the TLR4/JAK/STAT1 signaling pathway promotes the acetylation of high mobility group box 1 (HMGB1) in lipopolysaccharide‐activated macrophages
title Degradation of histone deacetylase 4 via the TLR4/JAK/STAT1 signaling pathway promotes the acetylation of high mobility group box 1 (HMGB1) in lipopolysaccharide‐activated macrophages
title_full Degradation of histone deacetylase 4 via the TLR4/JAK/STAT1 signaling pathway promotes the acetylation of high mobility group box 1 (HMGB1) in lipopolysaccharide‐activated macrophages
title_fullStr Degradation of histone deacetylase 4 via the TLR4/JAK/STAT1 signaling pathway promotes the acetylation of high mobility group box 1 (HMGB1) in lipopolysaccharide‐activated macrophages
title_full_unstemmed Degradation of histone deacetylase 4 via the TLR4/JAK/STAT1 signaling pathway promotes the acetylation of high mobility group box 1 (HMGB1) in lipopolysaccharide‐activated macrophages
title_short Degradation of histone deacetylase 4 via the TLR4/JAK/STAT1 signaling pathway promotes the acetylation of high mobility group box 1 (HMGB1) in lipopolysaccharide‐activated macrophages
title_sort degradation of histone deacetylase 4 via the tlr4/jak/stat1 signaling pathway promotes the acetylation of high mobility group box 1 (hmgb1) in lipopolysaccharide‐activated macrophages
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6026695/
https://www.ncbi.nlm.nih.gov/pubmed/29988587
http://dx.doi.org/10.1002/2211-5463.12456
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