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The non-antibiotic macrolide EM900 attenuates HDM and poly(I:C)-induced airway inflammation with inhibition of macrophages in a mouse model
OBJECTIVE: Macrolides have been reported to reduce the exacerbation of severe asthma. The aim of this study was to clarify the effects and mechanisms of EM900, a non-antibiotic macrolide, on allergic airway inflammation. METHODS: Mice were sensitized and challenged by house dust mite (HDM), then exp...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942021/ https://www.ncbi.nlm.nih.gov/pubmed/31820024 http://dx.doi.org/10.1007/s00011-019-01302-3 |
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author | Sadamatsu, Hironori Takahashi, Koichiro Tashiro, Hiroki Kato, Go Noguchi, Yoshihiko Kurata, Keigo Ōmura, Satoshi Kimura, Shinya Sunazuka, Toshiaki Sueoka-Aragane, Naoko |
author_facet | Sadamatsu, Hironori Takahashi, Koichiro Tashiro, Hiroki Kato, Go Noguchi, Yoshihiko Kurata, Keigo Ōmura, Satoshi Kimura, Shinya Sunazuka, Toshiaki Sueoka-Aragane, Naoko |
author_sort | Sadamatsu, Hironori |
collection | PubMed |
description | OBJECTIVE: Macrolides have been reported to reduce the exacerbation of severe asthma. The aim of this study was to clarify the effects and mechanisms of EM900, a non-antibiotic macrolide, on allergic airway inflammation. METHODS: Mice were sensitized and challenged by house dust mite (HDM), then exposed to polyinosinic-polycytidylic acid (poly(I:C)) as a model of asthma complicated with viral infection. Mice were administered with EM900. Airway inflammation was assessed from inflammatory cells in bronchoalveolar lavage fluid (BALF) and cytokines in lung tissues. Lung interstitial macrophages were counted by flow cytometry. Cytokine production, phosphorylation of NF-κB, and p38 in macrophages were examined by ELISA and western blotting. RESULTS: Counts of cells in BALF and concentrations of IL-13, IL-5, RANTES, IL-17A, and MIP-2 were significantly decreased by EM900 compared to those without EM900. Percentages of lung interstitial macrophages were significantly decreased with EM900. Concentrations of IL-6, RANTES, and MIP-2 induced by HDM and poly(I:C) were significantly suppressed by EM900 through the suppression of NF-κB and p38 phosphorylation in macrophages. CONCLUSIONS: HDM and poly(I:C)-induced airway inflammation is attenuated by EM900 with the inhibition of lung interstitial macrophages. Clinical use of EM900 is expected, because EM900 has inhibitory effects against airway inflammation without inducing bacterial drug resistance. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00011-019-01302-3) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6942021 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-69420212020-01-16 The non-antibiotic macrolide EM900 attenuates HDM and poly(I:C)-induced airway inflammation with inhibition of macrophages in a mouse model Sadamatsu, Hironori Takahashi, Koichiro Tashiro, Hiroki Kato, Go Noguchi, Yoshihiko Kurata, Keigo Ōmura, Satoshi Kimura, Shinya Sunazuka, Toshiaki Sueoka-Aragane, Naoko Inflamm Res Original Research Paper OBJECTIVE: Macrolides have been reported to reduce the exacerbation of severe asthma. The aim of this study was to clarify the effects and mechanisms of EM900, a non-antibiotic macrolide, on allergic airway inflammation. METHODS: Mice were sensitized and challenged by house dust mite (HDM), then exposed to polyinosinic-polycytidylic acid (poly(I:C)) as a model of asthma complicated with viral infection. Mice were administered with EM900. Airway inflammation was assessed from inflammatory cells in bronchoalveolar lavage fluid (BALF) and cytokines in lung tissues. Lung interstitial macrophages were counted by flow cytometry. Cytokine production, phosphorylation of NF-κB, and p38 in macrophages were examined by ELISA and western blotting. RESULTS: Counts of cells in BALF and concentrations of IL-13, IL-5, RANTES, IL-17A, and MIP-2 were significantly decreased by EM900 compared to those without EM900. Percentages of lung interstitial macrophages were significantly decreased with EM900. Concentrations of IL-6, RANTES, and MIP-2 induced by HDM and poly(I:C) were significantly suppressed by EM900 through the suppression of NF-κB and p38 phosphorylation in macrophages. CONCLUSIONS: HDM and poly(I:C)-induced airway inflammation is attenuated by EM900 with the inhibition of lung interstitial macrophages. Clinical use of EM900 is expected, because EM900 has inhibitory effects against airway inflammation without inducing bacterial drug resistance. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00011-019-01302-3) contains supplementary material, which is available to authorized users. Springer International Publishing 2019-12-09 2020 /pmc/articles/PMC6942021/ /pubmed/31820024 http://dx.doi.org/10.1007/s00011-019-01302-3 Text en © The Author(s) 2019 Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Original Research Paper Sadamatsu, Hironori Takahashi, Koichiro Tashiro, Hiroki Kato, Go Noguchi, Yoshihiko Kurata, Keigo Ōmura, Satoshi Kimura, Shinya Sunazuka, Toshiaki Sueoka-Aragane, Naoko The non-antibiotic macrolide EM900 attenuates HDM and poly(I:C)-induced airway inflammation with inhibition of macrophages in a mouse model |
title | The non-antibiotic macrolide EM900 attenuates HDM and poly(I:C)-induced airway inflammation with inhibition of macrophages in a mouse model |
title_full | The non-antibiotic macrolide EM900 attenuates HDM and poly(I:C)-induced airway inflammation with inhibition of macrophages in a mouse model |
title_fullStr | The non-antibiotic macrolide EM900 attenuates HDM and poly(I:C)-induced airway inflammation with inhibition of macrophages in a mouse model |
title_full_unstemmed | The non-antibiotic macrolide EM900 attenuates HDM and poly(I:C)-induced airway inflammation with inhibition of macrophages in a mouse model |
title_short | The non-antibiotic macrolide EM900 attenuates HDM and poly(I:C)-induced airway inflammation with inhibition of macrophages in a mouse model |
title_sort | non-antibiotic macrolide em900 attenuates hdm and poly(i:c)-induced airway inflammation with inhibition of macrophages in a mouse model |
topic | Original Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942021/ https://www.ncbi.nlm.nih.gov/pubmed/31820024 http://dx.doi.org/10.1007/s00011-019-01302-3 |
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