Dimeric procyanidins as modulators of airway inflammation in the context of allergic asthma : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy (PhD) in Human Physiology at Massey University, Manawatū, Palmerston North, New Zealand
| dc.contributor.author | Coleman, Sara L | |
| dc.date.accessioned | 2017-11-07T00:54:53Z | |
| dc.date.available | 2017-11-07T00:54:53Z | |
| dc.date.issued | 2017 | |
| dc.description.abstract | Procyanidins are polyphenolic compounds that have come to be known as biologically active in the context of promoting human health. Epidemiological evidence suggests that populations that consume diets rich in procyanidins are less susceptible to inflammatory diseases. Allergic asthma is an inflammatory lung disease with an estimated 100 million affected individuals worldwide, with New Zealand having the world’s second highest rate. Inflammation at the airway epithelium and infiltration of immune cells, specifically eosinophils, into the lung tissue are two central characteristics of allergic asthma. Thymic stromal lymphopoietin (TSLP) and eotaxin isoforms, eotaxin-1 (CCL11) and eotaxin-3 (CCL26), are three biomarkers of airway inflammation produced by the epithelium. Cell culture models were successfully optimized for CCL11 and CCL26 production in A549 cells. Investigation of procyanidins effect on epithelial TSLP production was not possible because TSLP production in A549 cells was undetectable. Data suggests that dimeric A-type linked procyanidin A2, but not B-type linked procyanidin B1 or B2, is capable of inhibiting IL-4-induced CCL11 production when incubated on A549 cells prior to an inflammatory insult. Co-incubation of A549 cells with procyanidin A2 and procyanidin B2 demonstrated no evidence of a synergistic relationship for inhibiting cytokine- induced CCL11 production. Similarly, A549 cells exposed to procyanidin A2, and to a lesser extent procyanidin B2, had reduced production of cytokine-induced CCL26 production. An inhibition time course demonstrated procyanidin A2 had greatest inhibition efficacy on cytokine-induced CCL26 production when incubated for 2 h prior to an inflammatory insult. Comparison of procyanidin A2 inhibition to the known CCL26 inhibitor, IFN , demonstrated that procyanidin A2 and IFN did not share the same temporal inhibition patterns. Furthermore, experiments investigating concomitant incubation of procyanidin A2 and IFN demonstrated that procyanidin A2 could interfere with IFN –mediated CCL26 inhibition. Two possible mechanisms responsible for the procyanidin A–mediated inhibition of cytokine-induced CCL11 and CCL26 were investigated: the modulation of cytokine receptor expression, and modulation of plasma membrane fluidity. However, there was no evidence to support either of these modes of action. The data presented in this thesis collectively demonstrate the ability of procyanidin A2 to inhibit cytokine-induced eotaxin production from the lung epithelium in vitro and support further investigation of procyanidin A2 as a preventative approach for managing airway inflammation. | en_US |
| dc.identifier.uri | http://hdl.handle.net/10179/12291 | |
| dc.language.iso | en | en_US |
| dc.publisher | Massey University | en_US |
| dc.rights | The Author | en_US |
| dc.subject | Polyphenols | en_US |
| dc.subject | Physiological aspects | en_US |
| dc.subject | Airway (Medicine) | en_US |
| dc.subject | Inflammation | en_US |
| dc.subject | Respiratory allergy | en_US |
| dc.subject | Nutritional aspects | en_US |
| dc.subject | Research Subject Categories::MEDICINE::Physiology and pharmacology::Physiology | en_US |
| dc.title | Dimeric procyanidins as modulators of airway inflammation in the context of allergic asthma : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy (PhD) in Human Physiology at Massey University, Manawatū, Palmerston North, New Zealand | en_US |
| dc.type | Thesis | en_US |
| massey.contributor.author | Coleman, Sara | |
| thesis.degree.discipline | Human Physiology | en_US |
| thesis.degree.grantor | Massey University | en_US |
| thesis.degree.level | Doctoral | en_US |
| thesis.degree.name | Doctor of Philosophy (PhD) | en_US |
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