{'fraction_non_alphanumeric': 0.024035774175517048, 'fraction_numerical': 0.005030743432084964, 'mean_word_length': 5.438848920863309, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
SRC family kinase inhibition reduces NOX4 expression in bronchial epithelial cells from Idiopathic Pulmonary Fibrosis patients

Rationale: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease driven by continuous epithelial injury associated with a redox imbalance in the lungs. IPF is characterized by an increased oxidant production, primarily by NADPH oxidases (NOXes), as well as altered antioxidant defenses. NOX4 is highly upregulated in IPF lungs and associated with increased epithelial apoptosis. We have identified a role for NOX4 in the activation of SRC family kinases (SFK) that contributes to oxidant production and fibrotic gene expression. Aim of our study was to evaluate the effects of SFK inhibition on markers of cellular damage and inflammation in bronchial epithelial cells (HBE) from IPF patients. Methods: In this pilot study, HBE cells were isolated from epithelial lining fluid from controls (n=3) and IPF patients (n=4) by bronchoscopic microsampling and expanded. Next, NOX4 expression, SFK activation, cellular damage and pro-inflammatory cytokine secretion were evaluated in the absence or presence of SFK inhibitor saracatinib. Results: HBE cells from IPF patients had an increased expression of NOX4, which could be reduced by saracatinib by decreasing the phosphorylation and thus activation of SFK. This SFK inhibition in IPF-derived HBE cells also reduced cell damage shown by a lower LDH release and decreased gene expression of pro-apoptotic BAX. Furthermore, SFK inhibition reduced the significantly elevated secretion of pro-inflammatory cytokines IL-6 and IL-8 in IPF-derived HBE cells back to control levels. Conclusion: Our results suggest that saracatinib might be beneficial to explore as treatment strategy for IPF patients