0000000001115879
AUTHOR
Pilar Ribera
MUC1 deficiency mediates corticosteroid resistance in chronic obstructive pulmonary disease.
Background Lung inflammation in COPD is poorly controlled by inhaled corticosteroids (ICS). Strategies to improve ICS efficacy or the search of biomarkers who may select those patients candidates to receive ICS in COPD are needed. Recent data indicate that MUC1 cytoplasmic tail (CT) membrane mucin can mediate corticosteroid efficacy in chronic rhinosinusitis. The objective of this work was to analyze the previously unexplored role of MUC1 on corticosteroid efficacy in COPD in vitro and in vivo models. Methods MUC1-CT expression was measured by real time PCR, western blot, immunohistochemistry and immunofluorescence. The inflammatory mediators IL-8, MMP9, GM-CSF and MIP3α were measured by EL…
Activation of nuclear factor erythroid 2-related (Nrf2) system as a novel therapeutic approach in COPD
Background: Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory lung disease caused by chronic exposure to cigarette smoke. Oxidative stress is one of the most important mechanisms involved in the physiopathology of COPD. Nuclear Factor Erythroid 2-related (Nrf2) is critical in protection against oxidative stress by inducing expression of antioxidant genes and a decrease in its expression has been observed in COPD patients. Objective: The aim of this study was to characterise the effects of Bardoxolone, Omavexolone and Obacunone as antioxidant drugs in COPD. Methods: Peripheral blood neutrophils from COPD and healthy volunteers and Primary Human Bronchial Epithelial cells were i…
Roflumilast N- oxide combined with sildenafil reverses cellular remodeling on IPF models
Background: Idiopathic pulmonary fibrosis (IPF) is characterized by a rapid progressive lung decline and premature death after its diagnosis. Roflumilast displayed anti-fibrotic effects in animal and cellular models. Recent studies indicate that the combination of PDE4 and PDE5 inhibitors (sildenafil) potentiates anti-fibrotic properties of each drug, suggesting potential beneficts of this combination. Objectives: To study the effects from adding sildenafil to roflumilast N-oxide (RNO) inhibiting TGFβ1-induced human alveolar type II (AECII) epithelial-to-mesenchymal transition (EMT) and human fibrocyte to myofibroblast transition in vitro. Methods: AECII and fibrocytes were isolated from he…
IL-11 promotes pulmonary vascular remodeling and lung fibrosis through the activation of endothelial to mesenchymal transition
Background: Pulmonary hypertension (PH) in idiopathic pulmonary fibrosis (IPF) portends a poor prognosis and currently there is no approved therapy for hypoxemic PH. IL-11 is a novel lung fibrosis mediator but its role on vascular function is unknown. Objective: To analyze the role of IL-11 on pulmonary artery remodeling and lung fibrosis in vitro and in vivo. Methods: IL-11 expression was evaluated in pulmonary arteries and lung sections of control subjects and patients with IPF, IPF+PH and idiopathic PH (PAH). Human pulmonary artery endothelial cells and smooth muscle cells were stimulated with IL-11. Endothelial to mesenchymal transition was evaluated measuring the increase of mesenchyma…
Additional file 1: of MUC1 deficiency mediates corticosteroid resistance in chronic obstructive pulmonary disease
Figure S1. Acute cigarette smoke/ lipopolysaccharide lung inflammatory animal model showed resistance to dexamethasone improving lung resistance and bronchoalveolar inflammatory cell extravasation in Muc1 KO animals. Figure S2. IL-8 and IL-13 bronchoalveolar fluid content in Muc1 KO mice exposed to acute cigarette smoke/ lipopolysaccharide is resistant to dexamethasone. Figure S3. Inflammatory lung cell infiltration secondary to acute lipopolysaccharide/ cigarette smoke exposure is resistant to dexamethasone in MUC1 KO mice. (DOCX 1611 kb)