1. Blackcurrant proanthocyanidins augment IFN-gamma-induced suppression of IL-4 stimulated CCL26 secretion in alveolar epithelial cells.
- Author
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Hurst SM, McGhie TK, Cooney JM, Jensen DJ, Gould EM, Lyall KA, and Hurst RD
- Subjects
- Anti-Inflammatory Agents, Non-Steroidal analysis, Anti-Inflammatory Agents, Non-Steroidal chemistry, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Asthma prevention & control, Catechin analogs & derivatives, Catechin pharmacology, Cell Line, Chemokine CCL26, Chemokines, CC genetics, Epithelial Cells drug effects, Epithelial Cells metabolism, Fruit chemistry, Gene Expression Regulation drug effects, Humans, Interferon-gamma agonists, Interleukin-13 antagonists & inhibitors, Interleukin-13 pharmacology, Interleukin-4 antagonists & inhibitors, Osmolar Concentration, Phosphorylation drug effects, Plant Extracts chemistry, Proanthocyanidins analysis, Proanthocyanidins chemistry, Pulmonary Alveoli metabolism, RNA, Messenger metabolism, Recombinant Proteins pharmacology, STAT6 Transcription Factor metabolism, Time Factors, Chemokines, CC metabolism, Interferon-gamma pharmacology, Interleukin-4 pharmacology, Plant Extracts pharmacology, Proanthocyanidins pharmacology, Pulmonary Alveoli drug effects, Ribes chemistry
- Abstract
Epidemiological studies reveal that fruit consumption reduces the prevalence of airway inflammation and childhood asthma. In particular, blackcurrant polyphenolic extracts have been shown to alleviate lung inflammation. Since IL-4-stimulated eotaxin-3 (CCL26) secretion is a major factor in the continuous eosinophil recruitment observed in atopic asthma, our focus was to evaluate the effectiveness of blackcurrant polyphenolic compounds on CCL26 secretion in human alveolar epithelial cells. Our results indicate that a proanthocyanin-enriched blackcurrant extract (BC-P), but not anthocyanin-enriched blackcurrant extract suppressed both IL-4- and IL-13-stimulated CCL26 secretion in a dose-dependent manner. Furthermore pre-incubation of cells with BC-P caused a time-dependent suppression of IL-4-stimulated CCL26 secretion. Moreover, epigallocatechin (EGC), and to a lesser extent epicatechin, metabolites identified in the proanthocyanidin extract, suppressed IL-4-stimulated CCL26 secretion. EGC was also effective at reducing the cellular phosphorylated STAT-6/STAT-6 ratio. Furthermore, both BC-P and purified EGC potentiated the ability of IFN-gamma to suppress IL-4-stimulated CCL26 secretion. The progression of an allergic immune response is complex, identifying plant compounds that target specific cellular events and complement the body's own immune actions is important for the development of functional foods. Our findings support the potential for blackcurrant polyphenolic compounds to reduce eosinophil recruitment and alleviate eosinophilic-driven airway inflammation.
- Published
- 2010
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