Function-specific IL-17A and dexamethasone interactions in primary human airway epithelial cells
Siti Farah Rahmawati1,2,3, Rémon Vos1,3, I Sophie T Bos1,3
1Department of Molecular Pharmacology, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
Scientific Reports
|June 30, 2022
Summary
Interleukin-17A (IL-17A) in asthma reduces airway epithelial cell sensitivity to corticosteroids. While IL-17A promotes inflammation and mucus, corticosteroids partially restore barrier function but not inflammation.
Area of Science:
- * Respiratory Medicine
- * Immunology
- * Cell Biology
Background:
- * Asthma is characterized by elevated Interleukin-17A (IL-17A) levels.
- * IL-17A is implicated in reduced corticosteroid sensitivity in airway epithelium.
Purpose of the Study:
- * To investigate the detailed mechanisms behind IL-17A-induced corticosteroid insensitivity in human airway epithelial cells.
- * To analyze gene expression, barrier function, mucus production, and cytokine secretion.
Main Methods:
- * Primary human airway epithelial cells (hAECs) were treated with IL-17A and dexamethasone.
- * RNA sequencing was performed to analyze gene expression changes.
- * Barrier function, mucus volume, and cytokine levels were measured.
Main Results:
- * IL-17A significantly altered the expression of 2861 genes, with most changes unaffected by dexamethasone.
- * IL-17A induced inflammation, goblet cell metaplasia, and mucus production, which were corticosteroid-insensitive.
- * Dexamethasone reversed IL-17A-induced epithelial barrier disruption, linked to cilia-related gene expression.
Conclusions:
- * IL-17A induces function-specific corticosteroid insensitivity in airway epithelium.
- * Corticosteroids are ineffective against IL-17A-driven inflammation and mucus production.
- * Corticosteroids can restore epithelial barrier integrity despite IL-17A stimulation.
Related Concept Videos
01:24T Cell Types and Functions
1.4K
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
1.4K
01:25Antiasthma Drugs: Mast Cell Stabilizers and Anti-IgE Drugs
435
Asthma is a chronic respiratory condition for which new therapeutic avenues, including anti-inflammatory drugs like mast cell stabilizers and anti-IgE treatments, continue to be developed.
Mast cell stabilizers, such as cromolyn (also known as sodium cromoglycate) and nedocromil (Tilade), are effective drugs in asthma management. These stabilizers hinder histamine release by skillfully obstructing the activation of mast cells and other cellular entities. Notably, they navigate this task without...
Mast cell stabilizers, such as cromolyn (also known as sodium cromoglycate) and nedocromil (Tilade), are effective drugs in asthma management. These stabilizers hinder histamine release by skillfully obstructing the activation of mast cells and other cellular entities. Notably, they navigate this task without...
435
01:19Antiasthma Drugs: Leukotriene Modifiers
442
Leukotriene modifiers, or cysteinyl leukotriene receptor antagonists, are medications used to manage chronic asthma. These agents target specific inflammatory mediators produced during arachidonic acid metabolism, an essential process in generating inflammation in the body.
Leukotriene modifiers work through two distinct mechanisms:
Leukotriene modifiers work through two distinct mechanisms:
442