Airway Smooth Muscle Synthesis of Inflammatory Mediators

Author(s):  
Alison E. John ◽  
Deborah L. Clarke ◽  
Alan J. Knox ◽  
Karl Deacon
2003 ◽  
Vol 95 (2) ◽  
pp. 844-853 ◽  
Author(s):  
Darren J. Fernandes ◽  
Richard W. Mitchell ◽  
Oren Lakser ◽  
Maria Dowell ◽  
Alastair G. Stewart ◽  
...  

It is now accepted that a host of cytokines, chemokines, growth factors, and other inflammatory mediators contributes to the development of nonspecific airway hyperresponsiveness in asthma. Yet, relatively little is known about how inflammatory mediators might promote airway structural remodeling or about the molecular mechanisms by which they might exaggerate smooth muscle shortening as observed in asthmatic airways. Taking a deep inspiration, which provides relief of bronchodilation in normal subjects, is less effective in asthmatic subjects, and some have speculated that this deficiency stems directly from an abnormality of airway smooth muscle and results in airway hyperresponsiveness to constrictor agonists. Here, we consider some of the mechanisms by which inflammatory mediators might acutely or chronically induce changes in the contractile apparatus that in turn might contribute to hyperresponsive airways in asthma.


2015 ◽  
Vol 93 (3) ◽  
pp. 203-206 ◽  
Author(s):  
Christine R. Keenan ◽  
Michael J. Schuliga ◽  
Alastair G. Stewart

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.


Sign in / Sign up

Export Citation Format

Share Document