Asthma is a heterogeneous disease characterized by different endotypes/phenotypes. Th2/Th17 driven mixed granulocytic asthma is one of them and shows resistance to corticosteroid therapy. Bromodomain and extra-terminal (BET) proteins are required for differentiation of Th17 cells which play a pivotal role in neutrophilic inflammation. Therefore, we sought to characterize the differential effects of BET inhibitor versus corticosteroids, and their potential synergism in cockroach allergen extract (CE)-induced mixed granulocytic (eosinophilic and neutrophilic) mouse model of asthma having Th2/Th17 endotype. Effects of BET inhibitor, (+)JQ-1 alone and in combination with dexamethasone (Dexa) were assessed on airway inflammation as well as Th2/Th17 related airway immune responses in CE-induced mixed granulocytic asthma. Markers of steroid resistance [histone deacetylase 2 (HDAC2), and oxidative stress] were also assessed in the lungs of mice and primary human bronchial epithelial cells (HBECs). BET inhibitor, (+)JQ-1 abolished Th17 driven neutrophilic inflammation in CE-induced mixed granulocytic asthma. Dexa had limited effect on overall airway inflammation despite having significant reductions in Th2 driven immune responses. However, combination of (+)JQ-1 with Dexa completely blocked both Th2 and /Th17 driven immune responses in the lung which led to significant reductions in eosinophils, neutrophils, and mucin secretion. (+)JQ-1 also reversed CE- and IL-17A-induced decrease in HDAC2 expression in murine and human airway epithelial cells respectively.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bcp.2018.05.011 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Anti-IL-5 treatment, but not neutrophil interference, attenuates inflammation in a mixed granulocytic asthma mouse model, elicited by air pollution.
Respir Res
January 2025
Department of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Medical Research Building (MRB) II, Ghent University Hospital, 2 Floor, Corneel Heymanslaan 10, 9000, Ghent, Belgium.
Introduction: Diesel exhaust particles (DEP) have been proven to aggravate asthma pathogenesis. We previously demonstrated that concurrent exposure to house dust mite (HDM) and DEP in mice increases both eosinophils and neutrophils in bronchoalveolar lavage fluid (BALF) and also results in higher levels of neutrophil-recruiting chemokines and neutrophil extracellular trap (NET) formation compared to sole HDM, sole DEP or saline exposure. We aimed to evaluate whether treatment with anti-IL-5 can alleviate the asthmatic features in this mixed granulocytic asthma model.
View Article and Find Full Text PDFNeutrophil-to-lymphocyte ratio and short-term mortality in patients having anti-MDA5-positive dermatomyositis with interstitial lung disease: a retrospective study.
BMC Pulm Med
January 2025
Department of Key Laboratory of Ningxia Stem Cell and Regenerative Medicine, Institute of Medical Sciences, Department of Pulmonary and Critical Care Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, China.
Background: In this study, we aimed to explore the association between baseline and early changes in the neutrophil-to-lymphocyte ratio (NLR) and the 30-day mortality rate in patients having anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis with interstitial lung disease (DM-ILD).
Methods: Overall, 263 patients with anti-MDA5 DM-ILD from four centers in China were analyzed. Multivariate logistic regression analysis was used to evaluate the impact of baseline NLR on the 30-day mortality rate in patients with anti-MDA5-positive DM-ILD.
CD131 antagonism blocks inflammation, emphysema and fibrosis in an asthma-COPD overlap mouse model originating in early life.
Respirology
January 2025
School of Health and Biomedical Sciences, RMIT University, Melbourne, Victoria, Australia.
Background And Objective: Asthma-COPD overlap (ACO) is characterized by patients exhibiting features of both asthma and COPD. Currently, there is no specific treatment for ACO. This study aimed to investigate the therapeutic potential of targeting CD131, a shared receptor subunit for IL-3, IL-5 and GM-CSF, in ACO development and in preventing acute viral exacerbations.
View Article and Find Full Text PDFA population of c-kit IL-17A ILC2s in sputum from individuals with severe asthma supports ILC2 to ILC3 trans-differentiation.
Sci Transl Med
January 2025
Department of Medicine, McMaster University, Hamilton, ON L8N 3Z5, Canada.
In prednisone-dependent severe asthma, uncontrolled sputum eosinophilia is associated with increased numbers of group 2 innate lymphoid cells (ILC2s). These cells represent a relatively steroid-insensitive source of interleukin-5 (IL-5) and IL-13 and are considered critical drivers of asthma pathology. The abundance of ILC subgroups in severe asthma with neutrophilic or mixed granulocytic (both eosinophilic and neutrophilic) airway inflammation, prone to recurrent infective exacerbations, remains unclear.
View Article and Find Full Text PDFThe Role of Basophil Activation Test in the Diagnosis of Pediatric Egg Allergy in Turkey: A Comparison of Clinical and Laboratory Findings with Real-Life Data.
Allergol Immunopathol (Madr)
January 2025
Faculty of Medicine, Department of Pediatric Allergy and Immunology, Ondokuz Mayıs University, Samsun, Turkey.
Background: Egg allergy is among the most common food allergies in children, significantly affecting the dietary habits and quality of life of both the affected children and their families. This study aims to assess the clinical role of the Basophil Activation Test (BAT) in children with egg allergy and to evaluate its diagnostic accuracy in comparison to other tests.
Methods: The study included 46 children with egg allergy.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!