Unknown

Dataset Information

0

An essential regulatory role of downstream of kinase-1 in the ovalbumin-induced murine model of asthma.


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.

SUBMITTER: Lee CM 

PROVIDER: S-EPMC3326039 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

altmetric image

Publications


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 respo  ...[more]

Similar Datasets

2022-02-22 | GSE197090 | GEO
| S-EPMC4863152 | biostudies-literature
| S-EPMC7984926 | biostudies-literature
| S-EPMC3099436 | biostudies-literature
| S-EPMC4116401 | biostudies-literature
2014-02-02 | GSE27066 | GEO
| PRJNA808964 | ENA
| S-EPMC4214966 | biostudies-literature
| S-EPMC7402094 | biostudies-literature
2014-02-02 | E-GEOD-27066 | biostudies-arrayexpress