https://scholars.lib.ntu.edu.tw/handle/123456789/567934
標題: | Lentiviral-mediated GATA-3 RNAi decreases allergic airway inflammation and hyperresponsiveness | 作者: | Lee C.-C. Huang H.-Y. BOR-LUEN CHIANG |
公開日期: | 2008 | 出版社: | Nature Publishing Group | 卷: | 16 | 期: | 1 | 起(迄)頁: | 60-65 | 來源出版物: | Molecular Therapy | 摘要: | GATA-3 is the key transcriptional factor for Th2 commitment in T cells and is strongly associated with asthma and allergic disease. We studied the silencing of the GATA-3 gene expression using RNA interference (RNAi) delivered by a lentiviral vector, to evaluate the therapeutic role of GATA-3 short hairpin RNAs (shRNAs) in a murine model of asthma. Mice were sensitized with OVA and instilled intratracheally (IT) with GATA-3 shRNAs lentiviral vector (Lenti-si-GATA-3) once, 48 hours before challenge. After three challenges with the OVA antigen, the mice were assessed for airway hyperresponsiveness (AHR) and inflammation. With infection of Lenti-si-GATA-3 in EL-4 cells, GATA-3 gene expression was abrogated and downstream Th2 cytokines, such as interleukin-4 (IL-4) and IL-5, were also significantly inhibited. IT delivery of Lenti-si-GATA-3 in OVA-immunized mice resulted in a strong inhibition of local GATA-3 gene expression. Treatment with Lenti-si-GATA-3 successfully alleviated OVA-induced airway eosinophilia and Th2 cytokine release. While evaluating AHR by means of enhanced pause (Penh) and pulmonary resistance (RL) using body plethysmography, it was found that the administration of Lenti-si-GATA-3 had significantly decreased AHR in OVA-immunized mice. These results suggest that inhibition of GATA-3 gene expression by shRNAs lentiviral vectors strongly attenuates antigen-induced airway inflammation and hyper-responsiveness in mice. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-37549010258&doi=10.1038%2fsj.mt.6300309&partnerID=40&md5=b2f8d81981cced3fd6ba35fb96fbab65 https://scholars.lib.ntu.edu.tw/handle/123456789/567934 |
ISSN: | 1525-0016 | DOI: | 10.1038/sj.mt.6300309 | SDG/關鍵字: | antigen; interleukin 4; interleukin 5; lentivirus vector; short hairpin RNA; transcription factor GATA 3; allergic asthma; animal cell; animal experiment; animal model; animal tissue; antiinflammatory activity; article; body plethysmography; cancer cell culture; controlled study; cytokine release; female; gene silencing; hypersensitivity reaction; Loeffler pneumonia; lung resistance; mouse; nonhuman; RNA interference; Th2 cell; viral gene delivery system; Murinae; Mus |
顯示於: | 醫學系 |
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