- Title
- Inhibiting AKT phosphorylation employing non-cytotoxic anthraquinones ameliorates TH2 mediated allergic airways disease and rhinovirus exacerbation
- Creator
- Cesar de Souza Alves, Caio; Collison, Adam; Ferreira, Ana Paula; Mattes, Joerg; Hatchwell, Luke; Plank, Maximilian; Morten, Matthew; Foster, Paul S.; Johnston, Sebastian L.; da Costa, Cristiane França; de Almeida, Mauro Vieira; Teixeira, Henrique Couto
- Relation
- NHMRC
- Relation
- PLoS One Vol. 8, Issue 11
- Publisher Link
- http://dx.doi.org/10.1371/journal.pone.0079565
- Publisher
- Public Library of Science
- Resource Type
- journal article
- Date
- 2013
- Description
- Background: Severe asthma is associated with T helper (TH) 2 and 17 cell activation, airway neutrophilia and phosphoinositide-3-kinase (PI3K) activation. Asthma exacerbations are commonly caused by rhinovirus (RV) and also associated with PI3K-driven inflammation. Anthraquinone derivatives have been shown to reduce PI3K-mediated AKT phosphorylation in-vitro. Objective: To determine the anti-inflammatory potential of anthraquinones in-vivo. Methods: BALB/c mice were sensitized and challenged with crude house dust mite extract to induce allergic airways disease and treated with mitoxantrone and a novel non-cytotoxic anthraquinone derivative. Allergic mice were also infected with RV1B to induce an exacerbation. Results: Anthraquinone treatment reduced AKT phosphorylation, hypoxia-inducible factor-1α and vascular endothelial growth factor expression, and ameliorated allergen- and RV-induced airways hyprereactivity, neutrophilic and eosinophilic inflammation, cytokine/chemokine expression, mucus hypersecretion, and expression of TH2 proteins in the airways. Anthraquinones also boosted type 1 interferon responses and limited RV replication in the lung. Conclusion: Non-cytotoxic anthraquinone derivatives may be of therapeutic benefit for the treatment of severe and RV-induced asthma by blocking pro-inflammatory pathways regulated by PI3K/AKT.
- Subject
- asthma; mitoxantrone; anthraquinone; AKT phosphorylation
- Identifier
- http://hdl.handle.net/1959.13/1051005
- Identifier
- uon:15239
- Identifier
- ISSN:1932-6203
- Rights
- © 2013 Cesar de Souza Alves et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
- Language
- eng
- Full Text
- Reviewed
- Hits: 11355
- Visitors: 11637
- Downloads: 353
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT01 | Publisher version (open access) | 1 MB | Adobe Acrobat PDF | View Details Download |