title: Pro-inflammatory mediators increase levels of the noncoding RNA GAS5 in airway smooth muscle and epithelial cells.
abstract: The long noncoding RNA (lncRNA) GAS5 has been found to act as a decoy for the glucocorticoid receptor (GR), thus implicating GAS5 as a potential regulator of glucocorticoid sensitivity and resistance. Airway smooth muscle (ASM) cells and airway epithelial cells (AEC) play an important role in the pathogenesis and persistence of asthma and other chronic airways diseases. These airway structural cell types are also important cellular targets of the anti-inflammatory actions of glucocorticoids. In this study, we sought to examine the relevance of GAS5 to glucocorticoid sensitivity and resistance in ASM and AEC. We provide the first evidence that pro-inflammatory mediators up-regulate GAS5 levels in both airway epithelial and smooth muscle cells, and that decreasing GAS5 levels can enhance glucocorticoid action in AEC.
authors.affiliation: Lung Health Research Centre, Department of Pharmacology and Therapeutics, University of Melbourne, Grattan Street, Parkville, Victoria 3010, Australia.
authors.forename: Christine R
authors.initials: CR
authors.lastname: Keenan
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Schuliga
authors.forename: Alastair G
authors.initials: AG
authors.lastname: Stewart
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D015735:Mifepristone / Q000494:pharmacology; D009130:Muscle, Smooth / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; C561567:GAS5 long non-coding RNA, human; D062085:RNA, Long Noncoding; D015735:Mifepristone; D003907:Dexamethasone
keywords: ARN non codant; ARNnc; airway inflammation; glucocorticoid; glucocorticoïde; inflammatoire des voies respiratoires; lncRNA; non-coding RNA; résistance aux stéroïdes; steroid resistance