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Inhibition of phosphodiesterase 4 modulates cytokine induction from toll like receptor activated, but not rhinovirus infected, primary human airway smooth muscle
BACKGROUND: Virus-induced exacerbations of Chronic Obstructive Pulmonary Disease (COPD) are a significant health burden and occur even in those receiving the best current therapies. Rhinovirus (RV) infections are responsible for half of all COPD exacerbations. The mechanism by which exacerbations oc...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3832400/ https://www.ncbi.nlm.nih.gov/pubmed/24237854 http://dx.doi.org/10.1186/1465-9921-14-127 |
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author | Van Ly, David De Pedro, Monique James, Peter Morgan, Lucy Black, Judith L Burgess, Janette K Oliver, Brian GG |
author_facet | Van Ly, David De Pedro, Monique James, Peter Morgan, Lucy Black, Judith L Burgess, Janette K Oliver, Brian GG |
author_sort | Van Ly, David |
collection | PubMed |
description | BACKGROUND: Virus-induced exacerbations of Chronic Obstructive Pulmonary Disease (COPD) are a significant health burden and occur even in those receiving the best current therapies. Rhinovirus (RV) infections are responsible for half of all COPD exacerbations. The mechanism by which exacerbations occur remains undefined, however it is likely to be due to virus-induced inflammation. Given that phophodiesterase 4 (PDE(4)) inhibitors have an anti-inflammatory effect in patients with COPD they present a potential therapy prior to, and during, these exacerbations. METHODS: In the present study we investigated whether the PDE(4) inhibitor piclamilast (10(-6) M) could alter RV or viral mimetic (5 μg/mL of imiquimod or poly I:C) induced inflammation and RV replication in primary human airway smooth muscle cells (ASMC) and bronchial epithelial cells (HBEC). The mediators IL-6, IL-8, prostaglandin E(2) and cAMP production were assayed by ELISA and RV replication was assayed by viral titration. RESULTS: We found that in ASMCs the TLR3 agonist poly I:C induced IL-8 release was reduced while induced IL-6 release by the TLR7/8 agonist imiquimod was further increased by the presence of piclamilast. However, in RV infected ASMCs, virus replication and induced mediator release were unaltered by piclamilast, as was also found in HBECs. The novel findings of this study reveal that although PDE inhibitors may not influence RV-induced cytokine production in ASMCs and replication in either ASMCs or HBECs, they have the capacity to be anti-inflammatory during TLR activation by modulating the induction of these chemotactic cytokines. CONCLUSION: By extrapolating our in vitro findings to exacerbations of COPD in vivo this suggests that PDE(4) inhibitors may have beneficial anti-inflammatory properties when patients are infected with bacteria or viruses other than RV. |
format | Online Article Text |
id | pubmed-3832400 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-38324002013-11-19 Inhibition of phosphodiesterase 4 modulates cytokine induction from toll like receptor activated, but not rhinovirus infected, primary human airway smooth muscle Van Ly, David De Pedro, Monique James, Peter Morgan, Lucy Black, Judith L Burgess, Janette K Oliver, Brian GG Respir Res Research BACKGROUND: Virus-induced exacerbations of Chronic Obstructive Pulmonary Disease (COPD) are a significant health burden and occur even in those receiving the best current therapies. Rhinovirus (RV) infections are responsible for half of all COPD exacerbations. The mechanism by which exacerbations occur remains undefined, however it is likely to be due to virus-induced inflammation. Given that phophodiesterase 4 (PDE(4)) inhibitors have an anti-inflammatory effect in patients with COPD they present a potential therapy prior to, and during, these exacerbations. METHODS: In the present study we investigated whether the PDE(4) inhibitor piclamilast (10(-6) M) could alter RV or viral mimetic (5 μg/mL of imiquimod or poly I:C) induced inflammation and RV replication in primary human airway smooth muscle cells (ASMC) and bronchial epithelial cells (HBEC). The mediators IL-6, IL-8, prostaglandin E(2) and cAMP production were assayed by ELISA and RV replication was assayed by viral titration. RESULTS: We found that in ASMCs the TLR3 agonist poly I:C induced IL-8 release was reduced while induced IL-6 release by the TLR7/8 agonist imiquimod was further increased by the presence of piclamilast. However, in RV infected ASMCs, virus replication and induced mediator release were unaltered by piclamilast, as was also found in HBECs. The novel findings of this study reveal that although PDE inhibitors may not influence RV-induced cytokine production in ASMCs and replication in either ASMCs or HBECs, they have the capacity to be anti-inflammatory during TLR activation by modulating the induction of these chemotactic cytokines. CONCLUSION: By extrapolating our in vitro findings to exacerbations of COPD in vivo this suggests that PDE(4) inhibitors may have beneficial anti-inflammatory properties when patients are infected with bacteria or viruses other than RV. BioMed Central 2013 2013-11-15 /pmc/articles/PMC3832400/ /pubmed/24237854 http://dx.doi.org/10.1186/1465-9921-14-127 Text en Copyright © 2013 Van Ly et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Van Ly, David De Pedro, Monique James, Peter Morgan, Lucy Black, Judith L Burgess, Janette K Oliver, Brian GG Inhibition of phosphodiesterase 4 modulates cytokine induction from toll like receptor activated, but not rhinovirus infected, primary human airway smooth muscle |
title | Inhibition of phosphodiesterase 4 modulates cytokine induction from toll like receptor activated, but not rhinovirus infected, primary human airway smooth muscle |
title_full | Inhibition of phosphodiesterase 4 modulates cytokine induction from toll like receptor activated, but not rhinovirus infected, primary human airway smooth muscle |
title_fullStr | Inhibition of phosphodiesterase 4 modulates cytokine induction from toll like receptor activated, but not rhinovirus infected, primary human airway smooth muscle |
title_full_unstemmed | Inhibition of phosphodiesterase 4 modulates cytokine induction from toll like receptor activated, but not rhinovirus infected, primary human airway smooth muscle |
title_short | Inhibition of phosphodiesterase 4 modulates cytokine induction from toll like receptor activated, but not rhinovirus infected, primary human airway smooth muscle |
title_sort | inhibition of phosphodiesterase 4 modulates cytokine induction from toll like receptor activated, but not rhinovirus infected, primary human airway smooth muscle |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3832400/ https://www.ncbi.nlm.nih.gov/pubmed/24237854 http://dx.doi.org/10.1186/1465-9921-14-127 |
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