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

In this study, we have identified STAT-3 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 cellular pathway for STAT-3 activation. Poultry dust extract activated STAT-3 phosphorylation in Beas2B and normal human bronchial epithelial cells and in mouse lungs. Chemical inhibition and siRNA knockdown of STAT-3 suppressed induction of immune and inflammatory mediator levels. Antioxidants suppressed increase of STAT-3 phosphorylation by poultry dust extract indicating that oxidative stress is important for the activation. Chemical inhibition and siRNA knockdown experiments demonstrated that STAT-3 activation is dependent on the activation of Tyk2 and EGFR tyrosine kinases. Our studies show that poultry dust extract controls the induction of immune and inflammatory mediator levels via a cellular pathway involving oxidative stress mediated STAT-3 activation by Tyk2 and EGFR tyrosine kinases.
PMID: 31042082 [PubMed - as supplied by publisher]

Source: Am J Physiol Lung Ce... - April 30, 2019 Category: Respiratory Medicine Authors: Natarajan K, Meganathan V, Mitchell CT, Boggaram V Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research