RT Journal Article
SR Electronic
T1 EGR-1 as a potential biomarker in asthma and proinflammatory responses in airway epithelium
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP PA2041
DO 10.1183/13993003.congress-2021.PA2041
VO 58
IS suppl 65
A1 Golebski, Kornel
A1 Gorenjak, Mario
A1 Kabesch, Michael
A1 Maitland-Van Der Zee, Anke-Hilse
A1 Melén, Erik
A1 Potočnik, Uroš
A1 Reinartz, Susanne
A1 Valente, Elisangela Santos
A1 Vijverberg, Susanne
A1 Van Drunen, Cornelis
YR 2021
UL https://publications.ersnet.org//content/58/suppl_65/PA2041.abstract
AB Background: Establishing biomarkers to predict asthma outcomes and therapeutic response has great clinical significance. GWAS studies and eQTL databases identified polymorphisms in the EGR1 gene associated with asthma characteristics. However, application of a biomarker in a clinical setting requires functional validation. We investigated if EGR-1 plays a role in: 1) deregulation of inflammatory responses of lung epithelium exposed to asthma triggers and 2) response to glucocorticoids.Methods: CRISPR-Cas9 technique was used for targeted knock-out of EGR-1 in NCI-H292 lung epithelium. Mutant cells were exposed to polyIC, house dust mite (HDM), grass pollen (GP), and dexamethasone. Production of inflammatory cytokines, epithelial barrier integrity, tissue regeneration potential as well as production of type 2 cytokines by innate lymphoid cells type 2 (ILC2) in an epithelial cell co-culture model were studied.Results: EGR-1 knockout in lung epithelium resulted in an increased production of pro-inflammatory mediators (IL-6, IL-8, GM-CSF, TNF-a, and IP-10) in response to polyIC, HDM, and GP. EGR-1-/- cells displayed reduced sensitivity to dexamethasone in suppressing responses to polyIC and allergens. EGR-1-/- cells also displayed increased permeability upon exposure to allergens, reduced expression of tight junction protein ZO-1, and decreased potential for tissue regeneration. Co-culture of EGR-1-/- epithelium exposed to polyIC or HDM with ILC2s resulted in increased IL-5/IL-13 production by ILC2s, as compared with ILC2s co-cultured with wild type epithelium.Conclusion: EGR-1 plays a critical role in mediating the exaggerated inflammatory responses of epithelium observed in asthmatic patients.FootnotesCite this article as: European Respiratory Journal 2021; 58: Suppl. 65, PA2041.This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).