An Essential Regulatory Role of Downstream of Kinase-1 in the Ovalbumin-Induced Murine Model of AsthmaReportar como inadecuado




An Essential Regulatory Role of Downstream of Kinase-1 in the Ovalbumin-Induced Murine Model of Asthma - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

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.



Autor: Chang-Min Lee, In Duk Jung, Kyung Tae Noh, Jun Sik Lee, Jin Wook Park, Deok Rim Heo, Jun Ho Park, Jeong Hyun Chang, Il-Whan Choi,

Fuente: http://plos.srce.hr/



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