Organic dust induces inflammatory gene expression in lung epithelial cells via ROS-dependent STAT-3 activation.

Exposure to dust in agricultural and animal environments, known as organic dust, is associated with the development of respiratory symptoms and respiratory diseases. Inflammation is a key feature of lung pathologies associated with organic dust exposure, and exposure to organic dust induces the expression of several immune and inflammatory mediators. However, information on transcription factors and cellular and molecular mechanisms controlling the production of immune and inflammatory mediators induced by organic dust is limited. In this study, we have identified as an important transcription factor controlling the induction of expression of immune and inflammatory mediators by poultry dust extracts in airway epithelial cells and in mouse lungs and delineated the cellular pathway for duanyu1813-3 activation. Poultry dust extract activated duanyu1813-3 phosphorylation in Beas2B and normal human bronchial epithelial cells and in mouse lungs. Chemical inhibition and siRNA knockdown of duanyu1813-3 suppressed induction of immune and inflammatory mediator expression. Antioxidants suppressed the increase of duanyu1813-3 phosphorylation induced by poultry dust extract indicating that oxidative stress [elevated reactive oxygen species levels] is important for the activation. Chemical inhibition and siRNA knockdown experiments demonstrated that duanyu1813-3 activation is dependent on the activation of nonreceptor tyrosine-protein kinase 2 (TYK2) and epidermal growth factor receptor (EGFR) tyrosine kinases. Our studies show that poultry dust extract controls the induction of immune and inflammatory mediator expression via a cellular pathway involving oxidative stress-mediated duanyu1813-3 activation by TYK2 and EGFR tyrosine kinases.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}