House dust mite potentiates capsaicin-evoked Ca2+ transients in mouse pulmonary sensory neurons via activation of protease-activated receptor-2

Qihai Gu, Lu Yuan Lee

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

House dust mite (HDM) is a major source of allergen in house dust and has been suggested to be involved in the pathogenesis of asthma. In this study, we aimed to investigate whether HDM can modulate the sensitivity of pulmonary sensory neurons and, if so, to elucidate the underlying mechanism. Fura-2-based ratiometric Ca2+ imaging was carried out to determine the effect of HDM extract on the capsaicin-evoked Ca2+ transient in mouse vagal pulmonary sensory neurons. Pretreatment with HDM (50 μg ml-1, 5 min) significantly enhanced the Ca2+ transient evoked by capsaicin in these neurons isolated from wild-type mice. This potentiating effect of HDM was not antagonized by E-64, a selective cysteine protease inhibitor, but was completely prevented by AEBSF, a specific serine protease inhibitor. In addition, the potentiating effect of HDM on capsaicin-evoked Ca2+ transient was absent in the pulmonary sensory neurons isolated from protease-activated receptor-2 (PAR2) knockout mice. Furthermore, the sensitizing effect of HDM was completely abolished by U73122, a phosholipase C inhibitor, or chelerythrine, a protein kinase C inhibitor. In summary, our results demonstrate that HDM, mainly through its serine protease activity, potentiates capsaicin-evoked Ca2+ transient in mouse pulmonary sensory neurons via the activation of PAR2 and the phosholipase C-protein kinase C intracellular transduction cascade.

Original languageEnglish
Pages (from-to)534-543
Number of pages10
JournalExperimental Physiology
Volume97
Issue number4
DOIs
StatePublished - Apr 2012

ASJC Scopus subject areas

  • Physiology
  • Nutrition and Dietetics
  • Physiology (medical)

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