Proteome analysis of differential protein expression in allergen‐induced asthmatic mice lung after dexamethasone treatment

Abstract

Asthma has become substantially more prevalent in recent decades and is one of the foremost contributors to morbidity and mortality in industrialized countries. Corticosteroids are among the most effective medications for the treatment of asthma, but some patients do not respond well to corticosteroid treatment. In this study, we characterized the responses to an allergen and identified potential molecular targets of dexamethasone (Dex) treatment in acute asthma. Female BALB/c mice sensitized to ovalbumin (OVA) were challenged with aerosolized OVA for 1 week. During the challenge period, mice were treated daily with Dex by intraperitoneal injection. Phosphate-buffered saline treated and non-challenged mice served as control. Histological evaluation of OVA-induced mice revealed airway inflammation and goblet cell hyperplasia. In addition, interleukin 4 levels and interferon-gamma levels were increased and decreased, respectively. These changes were moderated by Dex treatment. Protein expression profiles were compared in each experimental group by two-dimensional gel electrophoresis and identified using matrix-assisted laser desorption/ionization-time of flight/time of flight mass spectrometry. Some proteins were increased, while others were decreased by Dex treatment. These results indicated that the regulation of protein expression might play a role in the immunological and pathological development of asthma and could be targeted for therapeutic intervention. These results may assist in the development of quantitative diagnostic markers to monitor disease progression or responses to therapy using proteomic approaches.

A Dissociated Glucocorticoid Receptor Modulator Reduces Airway Hyperresponsiveness and Inflammation in a Mouse Model of Asthma

“…This concurs with the CpdA-induced suppression of Th2 cytokine production as demonstrated in this study for IL-4, IL-13, and IL-5 in BAL fluid. In parallel, both DEX and CpdA are able to restore OVA-suppressed Th1 cytokine IFN-g levels, which is in agreement with previous demonstrations for DEX (32). Of note, and in contrast to this model, in a rat model for experimental autoimmune neuritis, which is a Th1 cell-mediated inflammatory demyelinating disease of the peripheral nervous system, CpdA significantly reduced mRNA levels of IFN-g, but increased those of IL-4, suggesting that Th2 cell polarization is favored by CpdA in this context (31).…”

Proteomic biomarker discovery for the monogenic disease cystic fibrosis

“…A number of proteomics studies have been performed on mice as a model for lung inflammations other than CF [79][80][81]. The first preliminary results reported by us, using a 2DE gelfree proteomic approach on laser-dissected cells from proximal bronchial epithelium of a transgenic CF mouse that was homozygous for F508del, proved promising and confirmed our idea that proteomics of a CF model mice will certainly give important hints to CF lung pathology [82].…”

Genome-Wide Profiling of Antigen-Induced Time Course Expression Using Murine Models for Acute and Chronic Asthma

“…In our previous studies, we have successfully employed a similar model system to investigate changes in the protein expression profiles of plasma from chronically challenged mice and in the lungs of the dexamethasone-treated acute asthma mice [13, 14]. In this study, the animals were inhalationally challenged with a controlled level of aerosolized antigen for up to 9 weeks to produce acute and chronic mouse models.…”