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Acute cigarette smoke or extract exposure rapidly activates TRPA1-mediated calcium influx in primary human airway smooth muscle cells

Lookup NU author(s): JinHeng Lin, Professor Michael TaggartORCiD, Dr Lee Borthwick, Professor Andrew FisherORCiD, Dr Malcolm Brodlie, Dr Michael Gray

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© 2021, The Author(s).Tobacco smoking is the largest risk factor for developing chronic obstructive pulmonary disease (COPD), and is associated with hyperresponsiveness of airway smooth muscle (ASM). Chronic exposure to cigarette smoke (CS) leads to airway inflammation and remodelling. However, the direct effect of gaseous CS or CS extract (CSE) on human airway smooth muscle cell (hASMC) function remains poorly understood. This study investigated the acute effect of CS/CSE on calcium homeostasis, a key regulator of ASM physiology and pathophysiology. Primary hASMC were isolated from non-smoking donor lungs, and subjected to Ca2+ imaging studies. We found that both CS, and CSE, rapidly elevated cytosolic Ca2+ in hASMC through stimulation of plasmalemmal Ca2+ influx, but excluded store-operated and L-type Ca2+ channels as mediators of this effect. Using a specific pharmacological inhibitor, or shRNA-driven knockdown, we established that both CS and CSE stimulated Ca2+ influx in hASMC through the neurogenic pain receptor channel, transient receptor potential ankyrin 1 (TRPA1). CS/CSE-dependent, TRPA1-mediated Ca2+ influx led to myosin light-chain phosphorylation, a key process regulating ASM contractility. We conclude that TRPA1 is likely an important link between CS/CSE exposure and airway hyperresponsiveness, and speculate that acute CS/CSE-induced Ca2+ influx could lead to exacerbated ASM contraction and potentially initiate further chronic pathological effects of tobacco smoke.

Publication metadata

Author(s): Lin JH, Taggart M, Borthwick L, Fisher A, Brodlie M, Sassano MF, Tarran R, Gray MA

Publication type: Article

Publication status: Published

Journal: Scientific Reports

Year: 2021

Volume: 11

Issue: 1

Online publication date: 05/05/2021

Acceptance date: 19/04/2021

Date deposited: 04/06/2021

ISSN (electronic): 2045-2322

Publisher: Nature Research

URL: https://doi.org/10.1038/s41598-021-89051-4

DOI: 10.1038/s41598-021-89051-4

PubMed id: 33953304

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