House dust mite allergens induce Ca2+ signalling and alarmin responses in asthma airway epithelial cells

Xuan Ouyang, James A. Reihill, Lisa E.J. Douglas, Orla M. Dunne, Gerard P Sergeant, S. Lorraine Martin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

Type 2 inflammation in asthma develops with exposure to stimuli to include inhaled allergens from house dust mites (HDM). Features include mucus hypersecretion and the formation of pro-secretory ion transport characterised by elevated basal Cl current. Studies using human sinonasal epithelial cells treated with HDM extract report a higher protease activated receptor-2 (PAR-2) agonist-induced calcium mobilisation that may be related to airway sensitisation by allergen-associated proteases. Herein, this study aimed to investigate the effect of HDM on Ca2+ signalling and inflammatory responses in asthmatic airway epithelial cells. Primary bronchial epithelial cells (hPBECs) from asthma donors cultured at air-liquid interface were used to assess electrophysiological, Ca2+ signalling and inflammatory responses. Differences were observed regarding Ca2+ signalling in response to PAR-2 agonist 2-Furoyl-LIGRLO-amide (2-FLI), and equivalent short-circuit current (Ieq) in response to trypsin and 2-FLI, in ALI-asthma and healthy hPBECs. HDM treatment led to increased levels of intracellular cations (Ca2+, Na+) and significantly reduced the 2-FLI-induced change of Ieq in asthma cells. Apical HDM-induced Ca2+ mobilisation was found to mainly involve the activation of PAR-2 and PAR-4-associated store-operated Ca2+ influx and TRPV1. In contrast, PAR-2, PAR-4 antagonists and TRPV1 antagonist only showed slight impact on basolateral HDM-induced Ca2+ mobilisation. HDM trypsin-like serine proteases were the main components leading to non-amiloride sensitive Ieq and also increased interleukin-33 (IL-33) and thymic stromal lymphopoietin (TSLP) from asthma hPBECs. These studies add further insight into the complex mechanisms associated with HDM-induced alterations in cell signalling and their relevance to pathological changes within asthma.

Original languageEnglish
Article number167079
Number of pages14
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1870
Issue number4
Early online date20 Feb 2024
DOIs
Publication statusPublished - Apr 2024

Keywords

  • Asthma
  • Bronchial epithelial cells
  • House dust mite
  • Serine proteases
  • Trypsin-like proteases
  • PAR-2
  • PAR-4
  • TRPV1
  • IL-33
  • TSLP

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology

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