title: How the airway smooth muscle in cystic fibrosis reacts in proinflammatory conditions: implications for airway hyper-responsiveness and asthma in cystic fibrosis.
abstract: Among patients with cystic fibrosis there is a high prevalence (40-70%) of asthma signs and symptoms such as cough and wheezing and airway hyper-responsiveness to inhaled histamine or methacholine. Whether these abnormal airway responses are due to a primary deficiency in the cystic fibrosis transmembrane conductance regulator (CFTR) or are secondary to the inflammatory environment in the cystic fibrosis lungs is not clear. A role for the CFTR in smooth muscle function is emerging, and alterations in contractile signalling have been reported in CFTR-deficient airway smooth muscle. Persistent bacterial infection, especially with Pseudomonas aeruginosa, stimulates interleukin-8 release from the airway epithelium, resulting in neutrophilic inflammation. Increased neutrophilia and skewing of CFTR-deficient T-helper cells to type 2 helper T cells creates an inflammatory environment characterised by high concentrations of tumour necrosis factor α, interleukin-8, and interleukin-13, which might all contribute to increased contractility of airway smooth muscle in cystic fibrosis. An emerging role of interleukin-17, which is raised in patients with cystic fibrosis, in airway smooth muscle proliferation and hyper-responsiveness is apparent. Increased understanding of the molecular mechanisms responsible for the altered smooth muscle physiology in patients with cystic fibrosis might provide insight into airway dysfunction in this disease.
authors.affiliation: Meakins Christie Laboratories, McGill University Health Centre, Montreal, Quebec Canada.
authors.forename: Sarah
authors.initials: S
authors.lastname: McCuaig
authors.affiliation: Meakins Christie Laboratories, McGill University Health Centre, Montreal, Quebec Canada. Electronic address: james.martin@mcgill.ca.
authors.forename: James G
authors.initials: JG
authors.lastname: Martin
mesh_terms: D001249:Asthma / Q000175:diagnosis / Q000209:etiology / Q000276:immunology / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D020013:Calcium Signaling; D003550:Cystic Fibrosis / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007378:Interleukins / Q000378:metabolism; D009130:Muscle, Smooth / Q000378:metabolism / Q000503:physiopathology; D012137:Respiratory System / Q000378:metabolism / Q000503:physiopathology
chemical_list: D007378:Interleukins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator