- Title
- Role of antioxidants in rhinovirus-infected airway epithelial cells
- Creator
- Addnan, Faizul Helmi
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2013
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- Human rhinovirus are associated with the majority of exacerbations of asthma and chronic obstructive pulmonary disease. The epithelial cells of the airway are the primary target for invading rhinovirus and the alterations on the airway epithelium by the virus are believed to be central in enhancing the airway inflammation that leads to asthma exacerbations. The development of a conventional vaccine is not practical to fight against rhinovirus, due to the fact that there are more than 100 serotypes. Natural agents capable of interfering with viral replication warrant exploration, because as yet, no licensed effective antiviral is currently available. Hence, this thesis is conducted to provide a promising candidate against rhinovirus infection. We utilized natural potent antioxidant compounds including resveratrol, lycopene, zinc and vitamin D at physiologically relevant concentrations, to prevent inflammatory response of airway epithelial cells induced by rhinovirus. In this thesis, we studied the anti-inflammatory effect of resveratrol, lycopene, zinc and vitamin D against the major group of human rhinovirus, (consist of 90% rhinovirus serotypes) which is using intercellular adhesion molecule-1 on host cells to gain infection. We found that enriched Calu-3 cells with those antioxidant compounds prior to rhinovirus infection, significantly prevent the virus from replicating efficiently. However, the antioxidants failed to significantly decrease the inflammatory response of Calu-3 cells induced by rhinovirus. Rhinovirus infection cause significant secretion of interleukin-6, interleukin-8 and interferon-gamma-induced protein-10 into the cultured media, hence confirming the model used for investigating the effect of antioxidant compounds against the virus. Thorough mechanism studies to unfold antioxidants’ mode of action against rhinovirus replication were conducted. The study revealed that phosphotidyl inositol-3-kinase is required during RV internalisation, and enriched Calu-3 cells with resveratrol, lycopene and vitamin D decreased the activation level of phosphotidyl inositol-3-kinase, hence explained the significant decrease of viral titers observed earlier in the rhinovirus infection study. Verification studies were done using wortmannin which is a specific inhibitor of phosphotidyl inositol-3-kinase and visualizing AlexaFluor 555-labelled rhinovirus entry into Calu-3 cells by confocal microscopy. Antioxidant compounds were found not to have any significant effect in the course of viral translation and viral replication steps. Resveratrol, lycopene, vitamin D and zinc, were demonstrated to have beneficial roles in limiting rhinovirus replication in Calu-3 cells. Preventing or ameliorating rhinovirus replication will hopefully bring significant impact towards managing asthmatic patients who are at high risk of suffering rhinovirus-induced asthma exacerbations.
- Subject
- antioxidant; rhinovirus; resveratrol; vitamin D; lycopene; zinc; inflammation
- Identifier
- http://hdl.handle.net/1959.13/1041754
- Identifier
- uon:13954
- Rights
- Copyright 2013 Faizul Helmi Addnan
- Language
- eng
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| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT01 | Abstract | 68 KB | Adobe Acrobat PDF | View Details Download | ||
| View Details Download | ATTACHMENT02 | Thesis | 3 MB | Adobe Acrobat PDF | View Details Download |