Ritu Mann-Nüttel, Shivani Mandal, Marie Armbruster, Lakshmi Puttagunta, Paul Forsythe
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引用次数: 0
Abstract
Background: Pulmonary neuroendocrine cells (PNEC) are rare airway epithelial cells that have recently gained attention as potential amplifiers of allergic asthma. However, studying PNEC function in humans has been challenging due to a lack of cell isolation methods, and little is known about human PNEC function in response to asthma-relevant stimuli. Here we developed and characterized an in vitro human PNEC model and investigated the neuroendocrine response to extracts of the common aeroallergen house dust mite (HDM).
Methods: PNEC-enriched cultures were generated from human induced pluripotent stem cells (iPNEC) and primary bronchial epithelial cells (ePNEC). Characterized PNEC cultures were exposed to HDM extract, a volatile chemical odorant (Bergamot oil), or the bacterial membrane component, lipopolysaccharide (LPS), and neuroendocrine gene expression and neuropeptide release determined.
Results: Both iPNEC and ePNEC models demonstrated similar baseline neuroendocrine characteristics and a stimuli-specific modulation of gene expression. Most notably, exposure to HDM but not Bergamot oil or LPS, leads to dose-dependent induction of the CGRP encoding gene, CALCB, and corresponding release of the neuropeptide. HDM-induced CALCB expression and CGRP release could be inhibited by a protease-activated receptor 1 (PAR1) antagonist or protease inhibitors and was mimicked by a PAR1 agonist.
Conclusions: We have characterized a novel model of PNEC-enriched human airway epithelium and utilized this model to demonstrate a previously unrecognized role for human PNEC in mediating a direct neuroendocrine response to aeroallergen exposure.
期刊介绍:
Allergy is an international and multidisciplinary journal that aims to advance, impact, and communicate all aspects of the discipline of Allergy/Immunology. It publishes original articles, reviews, position papers, guidelines, editorials, news and commentaries, letters to the editors, and correspondences. The journal accepts articles based on their scientific merit and quality.
Allergy seeks to maintain contact between basic and clinical Allergy/Immunology and encourages contributions from contributors and readers from all countries. In addition to its publication, Allergy also provides abstracting and indexing information. Some of the databases that include Allergy abstracts are Abstracts on Hygiene & Communicable Disease, Academic Search Alumni Edition, AgBiotech News & Information, AGRICOLA Database, Biological Abstracts, PubMed Dietary Supplement Subset, and Global Health, among others.