The 5-azacytidine alleviated airway inflammation in OVA-sensitized mice and inhibited in vitro and in vivo T cell activation
| Autor: | Yi Hsin Chen, 陳意心 |
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| Rok vydání: | 2013 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 101 Asthma is a chronic inflammation disease of airways. Currently most therapeutic approaches still cannot provide effective cure for asthmatic patients. Regulatory T (Treg) cells play a central role in the maintenance of self-tolerance and immune homeostasis. Thus, the elevated numbers of Treg cells in asthmatic patients may suppress pathogenesis of asthma. Foxp3 transcription factor is responsible for the development and suppressive function of Treg cells. Furthermore, it has been accepted that demethylation of CpG island in foxp3 locus correlates with increased Foxp3 expression. We administrated 5-azacytidine (5-Aza), a hypomethylation agent, to treat OVA-sensitized asthmatic mice and to examine whether it would alleviate asthmatic responses by enhancing the percentages of Treg cells. In this study, 5-Aza suppressed symptoms of allergic asthma and also enhanced the percentages of Treg cells. Although higher percentages of Treg cells were detected in spleen, the suppressive ability of Treg cells in 5-Aza-treated mice was not enhanced. Since T helper cells play a central role in development of asthma, 5-Aza might suppress T cell proliferation and activation at the initial stage of asthma. Indeed, 5-Aza inhibited antigen-specific T cell proliferation in vitro and in vivo. These results indicated that alleviated inflammation of allergic asthma by 5-Aza treatment might be through the elevated Treg numbers in lymphoid tissues. Besides, the inhibition of allergen-specific T cell proliferation may contribute to the attenuation of inflammation. These findings may provide a potential therapy for asthmatic patients. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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