Cargando…

sRAGE alleviates neutrophilic asthma by blocking HMGB1/RAGE signalling in airway dendritic cells

Receptor for advanced glycation end products (RAGE) plays a role in inflammatory reactions. The soluble form of RAGE (sRAGE) acts as a decoy to inhibit interactions of RAGE with advanced glycation end products such as High mobility group box 1 (HMGB1). We have demonstrated that HMGB1 directs Th17 sk...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Fang, Su, Xin, Huang, Gang, Xin, Xiao-Feng, Cao, E-Hong, Shi, Yi, Song, Yong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5660212/
https://www.ncbi.nlm.nih.gov/pubmed/29079726
http://dx.doi.org/10.1038/s41598-017-14667-4
_version_ 1783274256013983744
author Zhang, Fang
Su, Xin
Huang, Gang
Xin, Xiao-Feng
Cao, E-Hong
Shi, Yi
Song, Yong
author_facet Zhang, Fang
Su, Xin
Huang, Gang
Xin, Xiao-Feng
Cao, E-Hong
Shi, Yi
Song, Yong
author_sort Zhang, Fang
collection PubMed
description Receptor for advanced glycation end products (RAGE) plays a role in inflammatory reactions. The soluble form of RAGE (sRAGE) acts as a decoy to inhibit interactions of RAGE with advanced glycation end products such as High mobility group box 1 (HMGB1). We have demonstrated that HMGB1 directs Th17 skewing by regulating dendritic cell (DC) functions in a previous study. However, the protective effects of HMGB1 blockade with sRAGE in the development of neutrophilic asthma remain unclear. Here, we showed that allergen challenge decreased expression of sRAGE in a murine model of neutrophilic asthma, correlating well with neutrophil counts and interleukin (IL)-17 production. When HMGB1 signalling was blocked by intratracheal administration of sRAGE before sensitisation, HMGB1 expression, neutrophilic inflammation, and Th17-type responses were reduced significantly. Anti-asthma effects of sRAGE were achieved by inhibition of RAGE and IL-23 expression in airway CD11c(+) antigen-presenting cells. Finally, we showed that sRAGE inhibited Th17 polarisation induced by recombinant HMGB1 (rHMGB1)-activated dendritic cells (DCs) in vitro. Adoptive transfer of rHMGB1-activated DCs was sufficient to restore airway inflammation, whereas transfer of rHMGB1 plus sRAGE-activated DCs significantly reduced neutrophilic inflammation. Thus, sRAGE prevents Th17-mediated airway inflammation in neutrophilic asthma at least partly by blocking HMGB1/RAGE signalling in DCs.
format Online
Article
Text
id pubmed-5660212
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-56602122017-11-01 sRAGE alleviates neutrophilic asthma by blocking HMGB1/RAGE signalling in airway dendritic cells Zhang, Fang Su, Xin Huang, Gang Xin, Xiao-Feng Cao, E-Hong Shi, Yi Song, Yong Sci Rep Article Receptor for advanced glycation end products (RAGE) plays a role in inflammatory reactions. The soluble form of RAGE (sRAGE) acts as a decoy to inhibit interactions of RAGE with advanced glycation end products such as High mobility group box 1 (HMGB1). We have demonstrated that HMGB1 directs Th17 skewing by regulating dendritic cell (DC) functions in a previous study. However, the protective effects of HMGB1 blockade with sRAGE in the development of neutrophilic asthma remain unclear. Here, we showed that allergen challenge decreased expression of sRAGE in a murine model of neutrophilic asthma, correlating well with neutrophil counts and interleukin (IL)-17 production. When HMGB1 signalling was blocked by intratracheal administration of sRAGE before sensitisation, HMGB1 expression, neutrophilic inflammation, and Th17-type responses were reduced significantly. Anti-asthma effects of sRAGE were achieved by inhibition of RAGE and IL-23 expression in airway CD11c(+) antigen-presenting cells. Finally, we showed that sRAGE inhibited Th17 polarisation induced by recombinant HMGB1 (rHMGB1)-activated dendritic cells (DCs) in vitro. Adoptive transfer of rHMGB1-activated DCs was sufficient to restore airway inflammation, whereas transfer of rHMGB1 plus sRAGE-activated DCs significantly reduced neutrophilic inflammation. Thus, sRAGE prevents Th17-mediated airway inflammation in neutrophilic asthma at least partly by blocking HMGB1/RAGE signalling in DCs. Nature Publishing Group UK 2017-10-27 /pmc/articles/PMC5660212/ /pubmed/29079726 http://dx.doi.org/10.1038/s41598-017-14667-4 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Zhang, Fang
Su, Xin
Huang, Gang
Xin, Xiao-Feng
Cao, E-Hong
Shi, Yi
Song, Yong
sRAGE alleviates neutrophilic asthma by blocking HMGB1/RAGE signalling in airway dendritic cells
title sRAGE alleviates neutrophilic asthma by blocking HMGB1/RAGE signalling in airway dendritic cells
title_full sRAGE alleviates neutrophilic asthma by blocking HMGB1/RAGE signalling in airway dendritic cells
title_fullStr sRAGE alleviates neutrophilic asthma by blocking HMGB1/RAGE signalling in airway dendritic cells
title_full_unstemmed sRAGE alleviates neutrophilic asthma by blocking HMGB1/RAGE signalling in airway dendritic cells
title_short sRAGE alleviates neutrophilic asthma by blocking HMGB1/RAGE signalling in airway dendritic cells
title_sort srage alleviates neutrophilic asthma by blocking hmgb1/rage signalling in airway dendritic cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5660212/
https://www.ncbi.nlm.nih.gov/pubmed/29079726
http://dx.doi.org/10.1038/s41598-017-14667-4
work_keys_str_mv AT zhangfang sragealleviatesneutrophilicasthmabyblockinghmgb1ragesignallinginairwaydendriticcells
AT suxin sragealleviatesneutrophilicasthmabyblockinghmgb1ragesignallinginairwaydendriticcells
AT huanggang sragealleviatesneutrophilicasthmabyblockinghmgb1ragesignallinginairwaydendriticcells
AT xinxiaofeng sragealleviatesneutrophilicasthmabyblockinghmgb1ragesignallinginairwaydendriticcells
AT caoehong sragealleviatesneutrophilicasthmabyblockinghmgb1ragesignallinginairwaydendriticcells
AT shiyi sragealleviatesneutrophilicasthmabyblockinghmgb1ragesignallinginairwaydendriticcells
AT songyong sragealleviatesneutrophilicasthmabyblockinghmgb1ragesignallinginairwaydendriticcells