ovalbumin and 3-methyladenine

Ferroptosis was reported to be involved in the occurrence and development of asthma. However, the potential mechanism underlying the role of ferroptosis in asthma remains unclear. In this study, we established the mouse asthma model following the ovalbumin (OVA) method in C57BL/6 mice and the cell model with IL-13 induction in bronchial epithelial cells (BEAS-2B cells). Treatment of ferrostatin-1 (Ferr-1) and 3-methyladenine (3-MA) decreased iron deposition in IL-13-induced BEAS-2B cells and lung tissues of asthma mice, opposite to that in bronchoalveolar lavage fluid (BALF). Meanwhile, excessive lipid peroxidation asthma model

Topics: Adenine; Animals; Asthma; Bronchi; Bronchoalveolar Lavage Fluid; Cell Line; Cyclohexylamines; Cytokines; Disease Models, Animal; Epithelial Cells; Ferroptosis; Humans; Injections, Intraperitoneal; Interleukin-13; Male; Mice; Mice, Inbred C57BL; Ovalbumin; Oxidative Stress; Phenylenediamines; Signal Transduction

Studies have shown autophagy participation in the immunopathology of inflammatory diseases. However, autophagy role in asthma and in eosinophil extracellular traps (EETs) release is poorly understood. Here, we attempted to investigate the autophagy involvement in EETs release and in lung inflammation in an experimental asthma model. Mice were sensitized with ovalbumin (OVA), followed by OVA challenge. Before the challenge with OVA, mice were treated with an autophagy inhibitor, 3-methyladenine (3-MA). We showed that 3-MA treatment decreases the number of eosinophils, eosinophil peroxidase (EPO) activity, goblet cells hyperplasia, proinflammatory cytokines, and nuclear factor kappa B (NFκB) p65 immunocontent in the lung. Moreover, 3-MA was able to improve oxidative stress, mitochondrial energy metabolism, and Na

Topics: Adenine; Animals; Anti-Asthmatic Agents; Asthma; Autophagy; Bronchoalveolar Lavage Fluid; Cytokines; Disease Models, Animal; Energy Metabolism; Eosinophil Peroxidase; Eosinophils; Extracellular Traps; Female; Goblet Cells; Lung; Mice; Mice, Inbred BALB C; Mitochondria; Ovalbumin; Oxidative Stress; Reactive Oxygen Species; Transcription Factor RelA

Statins have been widely used in inflammatory diseases including asthma, because of their anti-inflammatory and immunomodulatory properties. It has been shown that simvastatin induces autophagy and cell death in some circumstances. However, the possible cross-talk between simvastatin and autophagic processes in lung disease is largely unknown. Thus, we investigated the impact of simvastatin on airway inflammation and airway remodelling and the possible relationship of these processes to a simvastatin-induced autophagic pathway in mouse models of asthma.. Ovalbumin (OVA)-sensitized and challenged mice were treated with simvastatin and sacrificed. The autophagy-related proteins Atg5, LC3B and Beclin1 were quantified, as well as the autophagy flux in bronchial smooth muscle cells (BSMCs). The relationship between airway inflammation and the autophagic process was investigated.. We show that simvastatin treatment mediates activation of autophagy in BSMCs, which is correlated with airway inflammation and airway remodelling in mouse models of asthma. Simvastatin increases autophagy-related protein Atg5, LC3B and Beclin1 expression and autophagosome formation in lung tissue. Simvastatin-induced autophagy is associated with increased interferon-gamma (IFN-γ) and decreased IL-4, IL-5 and IL-13 cytokines production in BSMCs, as well as reversed extracellular matrix (ECM) deposition. In contrast, autophagy inhibitor 3-methyladenine (3-MA) eliminates the therapeutic effect of simvastatin.. These findings demonstrate that simvastatin inhibits airway inflammation and airway remodelling through an activated autophagic process in BSMCs. We propose a crucial function of autophagy in statin-based therapeutic approaches in asthma.

Topics: Adenine; Airway Remodeling; Animals; Asthma; Autophagosomes; Autophagy; Autophagy-Related Protein 5; Beclin-1; Cytokines; Disease Models, Animal; Extracellular Matrix; Female; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Interferon-gamma; Mice; Mice, Inbred BALB C; Microtubule-Associated Proteins; Myocytes, Smooth Muscle; Ovalbumin; Simvastatin; Up-Regulation