An Essential Regulatory Role of Downstream of Kinase-1 in the Ovalbumin-Induced Murine Model of Asthmaopen access
- Authors
- Lee, Chang-Min; Jung, In Duk; Noh, Kyung Tae; Lee, Jun Sik; Park, Jin Wook; Heo, Deok Rim; Park, Jun Ho; Chang, Jeong Hyun; Choi, Il-Whan; Kim, Jong-Suk; Shin, Yong Kyoo; Park, Sung-Joo; Han, Myung-Kwan; Lee, Chun Geun; Cho, Won-Kyung; Park, Yeong-Min
- Issue Date
- Apr-2012
- Publisher
- PUBLIC LIBRARY SCIENCE
- Citation
- PLOS ONE, v.7, no.4
- Journal Title
- PLOS ONE
- Volume
- 7
- Number
- 4
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/20378
- DOI
- 10.1371/journal.pone.0034554
- ISSN
- 1932-6203
- Abstract
- The downstream of kinase (DOK)-1 is involved in the protein tyrosine kinase (PTK) pathway in mast cells, but the role of DOK-1 in the pathogenesis of asthma has not been defined. In this study, we have demonstrated a novel regulatory role of DOK-1 in airway inflammation and physiologic responses in a murine model of asthma using lentiviral vector containing DOK-1 cDNA or DOK-1-specific ShRNA. The OVA-induced inflammatory cells, airway hyperresponsiveness, Th2 cytokine expression, and mucus response were significantly reduced in DOK-1 overexpressing mice compared to OVA-challenged control mice. The transgenic introduction of DOK-1 significantly stimulated the activation and expression of STAT-4 and T-bet, while impressively inhibiting the activation and expression of STAT-6 and GATA-3 in airway epithelial cells. On the other hand, DOK-1 knockdown mice enhanced STAT-6 expression and its nuclear translocation compared to OVA-challenged control mice. When viewed in combination, our studies demonstrate DOK-1 regulates allergen-induced Th2 immune responses by selective stimulation and inhibition of STAT-4 and STAT-6 signaling pathways, respectively. These studies provide a novel insight on the regulatory role of DOK-1 in allergen-induced Th2 inflammation and airway responses, which has therapeutic potential for asthma and other allergic diseases.
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