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

Airborne indoor allergen serine proteases and their contribution to sensitisation and activation of innate immunity in allergic airway disease

“…Serine proteases from HDM have been reported to increase epithelial IL-33, TSLP and IL-25 secretion, resulting in activation of ILC2s, which produce IL-5, IL-9 and IL-13, in addition to IL-5 from eosinophils [ 135 , 136 ]. Specifically, trypsin-like serine proteases have been identified to be the main allergen component of HDMs leading to the increased secretion of IL-33 and TSLP from asthma human primary bronchial epithelial cells (hPBECs) [ 137 ]. Upon exposure of epithelial cells to allergen proteases (fungi, cockroaches and mites), caspase-8 is activated via a novel signalling hub, the caspase-8 activating ripoptosome, a protein complex which consists of receptor-interacting serine/threonine-protein kinase 1 (RIPK1), Fas-associated via death domain and pro-caspase-8 [ 138 , 139 ].…”

“…Moreover, increased expression of PAR-2 has been observed in monocytes derived from patients with AR or asthma, thereby contributing to TNF-α expression. Asthma and healthy hPBECs grown at the ALI also show different Ca 2+ signalling in response to stimulation by HDM with the apical response of asthma airway cells thought to involve signalling via PAR-2, PAR-4 and TRPV1, transient receptor potential ankyrin 1 and TRPV4; the antagonist of these channels only had a small impact on basolateral HDM-induced Ca 2+ response [ 137 ]. It is also possible that other transient receptor potential channels such as TRPV2 (localised on the basolateral side) may play a role in the regulation of basolateral HDM-induced Ca 2+ mobilisation, thus further study is required.…”

“…Our group reported that a Bowman–Birk proteinase inhibitor (BBI)-type peptide isolated from skin secretions of the amphibian Pelophylax esculentus (PE) named PE-BBI [ 232 ], can selectively protect airway epithelial barrier function by directly inhibiting TLP activities in whole-body German cockroach extract (CRE), but had no effect on host protease activities [ 222 , 225 ]. The highly selective inhibition of allergen TLPs by PE-BBI also extends to HDM proteases where PE-BBI reduced HDM-induced Ca 2+ mobilisation in submerged cultures of asthma hPBECs, but did not affect subsequent Ca 2+ mobilisation induced by trypsin [ 137 ]. We also synthesised a series of peptide derivatives containing an N-alkyl glycine analogue of arginine.…”