{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T04:08:39Z","timestamp":1783829319155,"version":"3.55.0"},"reference-count":53,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,12,4]],"date-time":"2022-12-04T00:00:00Z","timestamp":1670112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Classically, the effects elicited by corticosteroids (CS) are mediated by the binding and activation of cytosolic glucocorticoid receptors (GR). However, several of the non-genomic effects of CS seem to be mediated by putative non-classic membrane receptors characterized by pharmacological properties that are different from those of classic cytosolic GR. Since pre-clinical findings suggest that inhaled CS (ICS) may also regulate the bronchial contractile tone via putative CS membrane-associate receptors, the aim of this review was to systematically report and discuss the impact of CS on human airway smooth muscle (ASM) contractility and airway hyperresponsiveness (AHR). Current evidence indicates that CS have significant genomic\/non-genomic beneficial effects on human ASM contractility and AHR, regardless of their anti-inflammatory effects. CS are effective in reducing either the expression, synthesis or activity of \u03b1-actin, CD38, inositol phosphate, myosin light chain kinase, and ras homolog family member A in response to several pro-contractile stimuli; overall these effects are mediated by the genomic action of CS. Moreover, CS elicited a strong bronchorelaxant effect via the rapid activation of the Gs\u03b1\u2013cyclic-adenosine-monophosphate\u2013protein-kinase-A pathway in hyperresponsive airways. The possibility of modulating the dose of the ICS in a triple ICS\/long-acting \u03b22-adrenoceptor agonist\/long-acting muscarinic antagonist fixed-dose combination supports the use of a Triple MAintenance and Reliever Therapy (TriMART) in those asthmatic patients at Step 3\u20135 who may benefit from a sustained bronchodilation and have been suffering from an increased parasympathetic tone.<\/jats:p>","DOI":"10.3390\/ijms232315285","type":"journal-article","created":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T02:13:12Z","timestamp":1670206392000},"page":"15285","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The Impact of Corticosteroids on Human Airway Smooth Muscle Contractility and Airway Hyperresponsiveness: A Systematic Review"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0456-069X","authenticated-orcid":false,"given":"Luigino","family":"Calzetta","sequence":"first","affiliation":[{"name":"Respiratory Disease and Lung Function Unit, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Chetta","sequence":"additional","affiliation":[{"name":"Respiratory Disease and Lung Function Unit, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0636-5345","authenticated-orcid":false,"given":"Marina","family":"Aiello","sequence":"additional","affiliation":[{"name":"Respiratory Disease and Lung Function Unit, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Pistocchini","sequence":"additional","affiliation":[{"name":"Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7801-5040","authenticated-orcid":false,"given":"Paola","family":"Rogliani","sequence":"additional","affiliation":[{"name":"Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.tips.2018.11.002","article-title":"Non-genomic Effects of Glucocorticoids: An Updated View","volume":"40","author":"Panettieri","year":"2019","journal-title":"Trends Pharmacol. 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