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Increased rhinovirus replication in nasal mucosa cells in allergic subjects is associated with increased ICAM‐1 levels and endosomal acidification and is inhibited by L‐carbocisteine

Increased viral replication and cytokine production may be associated with the pathogenesis of asthma attacks in rhinovirus (RV) infections. However, the association between increased RV replication and enhanced expression of intercellular adhesion molecule‐1 (ICAM‐1), a receptor for a major RV grou...

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Autores principales: Yamaya, Mutsuo, Nomura, Kazuhiro, Arakawa, Kazuya, Nishimura, Hidekazu, Lusamba Kalonji, Nadine, Kubo, Hiroshi, Nagatomi, Ryoichi, Kawase, Tetsuaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879463/
https://www.ncbi.nlm.nih.gov/pubmed/27957326
http://dx.doi.org/10.1002/iid3.102
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author Yamaya, Mutsuo
Nomura, Kazuhiro
Arakawa, Kazuya
Nishimura, Hidekazu
Lusamba Kalonji, Nadine
Kubo, Hiroshi
Nagatomi, Ryoichi
Kawase, Tetsuaki
author_facet Yamaya, Mutsuo
Nomura, Kazuhiro
Arakawa, Kazuya
Nishimura, Hidekazu
Lusamba Kalonji, Nadine
Kubo, Hiroshi
Nagatomi, Ryoichi
Kawase, Tetsuaki
author_sort Yamaya, Mutsuo
collection PubMed
description Increased viral replication and cytokine production may be associated with the pathogenesis of asthma attacks in rhinovirus (RV) infections. However, the association between increased RV replication and enhanced expression of intercellular adhesion molecule‐1 (ICAM‐1), a receptor for a major RV group, in airway epithelial cells has remained unclear. Furthermore, the inhibitory effects of mucolytics, which have clinical benefits in asthmatic subjects, are uncertain. Human nasal epithelial (HNE) cells were infected with type 14 rhinovirus (RV14), a major RV group. RV14 titers and cytokine concentrations, including interleukin (IL)‐6 and IL‐8, in supernatants, RV14 RNA replication and susceptibility to RV14 infection were higher in HNE cells obtained from subjects in the allergic group (allergic subjects) than in those from subjects in the non‐allergic group (non‐allergic subjects). ICAM‐1 expression and the number and fluorescence intensity of acidic endosomes from which RV14 RNA enters the cytoplasm were higher in HNE cells from allergic subjects, though substantial amounts of interferon (IFN)‐γ and IFN‐λ were not detected in the supernatant. The abundance of p50 and p65 subunits of transcription factor nuclear factor kappa B (NF‐κB) in nuclear extracts of the cells from allergic subjects was higher compared to non‐allergic subjects, and an inhibitor of NF‐κB, caffeic acid phenethyl ester, reduced the fluorescence intensity of acidic endosomes as well as RV titers and RNA. Furthermore, a mucolytic agent, L‐carbocisteine, reduced RV14 titers and RNA levels, cytokine release, ICAM‐1 expression, the fluorescence intensity of acidic endosomes, and NF‐κB activation. The increased RV14 replication observed in HNE cells from allergic subjects might be partly associated with enhanced ICAM‐1 expression and decreased endosomal pH through NF‐κB activation. L‐Carbocisteine inhibits RV14 infection by reducing ICAM‐1 and acidic endosomes and may, therefore, modulate airway inflammation caused by RV infection in allergic subjects.
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spelling pubmed-48794632016-12-12 Increased rhinovirus replication in nasal mucosa cells in allergic subjects is associated with increased ICAM‐1 levels and endosomal acidification and is inhibited by L‐carbocisteine Yamaya, Mutsuo Nomura, Kazuhiro Arakawa, Kazuya Nishimura, Hidekazu Lusamba Kalonji, Nadine Kubo, Hiroshi Nagatomi, Ryoichi Kawase, Tetsuaki Immun Inflamm Dis Original Research Increased viral replication and cytokine production may be associated with the pathogenesis of asthma attacks in rhinovirus (RV) infections. However, the association between increased RV replication and enhanced expression of intercellular adhesion molecule‐1 (ICAM‐1), a receptor for a major RV group, in airway epithelial cells has remained unclear. Furthermore, the inhibitory effects of mucolytics, which have clinical benefits in asthmatic subjects, are uncertain. Human nasal epithelial (HNE) cells were infected with type 14 rhinovirus (RV14), a major RV group. RV14 titers and cytokine concentrations, including interleukin (IL)‐6 and IL‐8, in supernatants, RV14 RNA replication and susceptibility to RV14 infection were higher in HNE cells obtained from subjects in the allergic group (allergic subjects) than in those from subjects in the non‐allergic group (non‐allergic subjects). ICAM‐1 expression and the number and fluorescence intensity of acidic endosomes from which RV14 RNA enters the cytoplasm were higher in HNE cells from allergic subjects, though substantial amounts of interferon (IFN)‐γ and IFN‐λ were not detected in the supernatant. The abundance of p50 and p65 subunits of transcription factor nuclear factor kappa B (NF‐κB) in nuclear extracts of the cells from allergic subjects was higher compared to non‐allergic subjects, and an inhibitor of NF‐κB, caffeic acid phenethyl ester, reduced the fluorescence intensity of acidic endosomes as well as RV titers and RNA. Furthermore, a mucolytic agent, L‐carbocisteine, reduced RV14 titers and RNA levels, cytokine release, ICAM‐1 expression, the fluorescence intensity of acidic endosomes, and NF‐κB activation. The increased RV14 replication observed in HNE cells from allergic subjects might be partly associated with enhanced ICAM‐1 expression and decreased endosomal pH through NF‐κB activation. L‐Carbocisteine inhibits RV14 infection by reducing ICAM‐1 and acidic endosomes and may, therefore, modulate airway inflammation caused by RV infection in allergic subjects. John Wiley and Sons Inc. 2016-04-15 /pmc/articles/PMC4879463/ /pubmed/27957326 http://dx.doi.org/10.1002/iid3.102 Text en © 2016 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (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 Original Research
Yamaya, Mutsuo
Nomura, Kazuhiro
Arakawa, Kazuya
Nishimura, Hidekazu
Lusamba Kalonji, Nadine
Kubo, Hiroshi
Nagatomi, Ryoichi
Kawase, Tetsuaki
Increased rhinovirus replication in nasal mucosa cells in allergic subjects is associated with increased ICAM‐1 levels and endosomal acidification and is inhibited by L‐carbocisteine
title Increased rhinovirus replication in nasal mucosa cells in allergic subjects is associated with increased ICAM‐1 levels and endosomal acidification and is inhibited by L‐carbocisteine
title_full Increased rhinovirus replication in nasal mucosa cells in allergic subjects is associated with increased ICAM‐1 levels and endosomal acidification and is inhibited by L‐carbocisteine
title_fullStr Increased rhinovirus replication in nasal mucosa cells in allergic subjects is associated with increased ICAM‐1 levels and endosomal acidification and is inhibited by L‐carbocisteine
title_full_unstemmed Increased rhinovirus replication in nasal mucosa cells in allergic subjects is associated with increased ICAM‐1 levels and endosomal acidification and is inhibited by L‐carbocisteine
title_short Increased rhinovirus replication in nasal mucosa cells in allergic subjects is associated with increased ICAM‐1 levels and endosomal acidification and is inhibited by L‐carbocisteine
title_sort increased rhinovirus replication in nasal mucosa cells in allergic subjects is associated with increased icam‐1 levels and endosomal acidification and is inhibited by l‐carbocisteine
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879463/
https://www.ncbi.nlm.nih.gov/pubmed/27957326
http://dx.doi.org/10.1002/iid3.102
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