Synthetic responses in airway smooth muscle

• Published in: Journal of Allergy and Clinical Immunology 2004-08, Vol.114 (2), p.S32-S50
• Main Authors: Howarth, Peter H, Knox, Alan J, Amrani, Yassine, Tliba, Omar, Panettieri, Reynold A, Johnson, Malcolm
• Format: Article
• Language: English
• Subjects: Adrenal Cortex Hormones - pharmacology; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists - pharmacology; airway remodeling; airway smooth muscle; Animals; Asthma; Asthma - etiology; Biological and medical sciences; Bronchi - cytology; Bronchi - drug effects; Chemokines; Chemokines - biosynthesis; chronic obstructive pulmonary disease; Collagen; corticosteroids; Cytokines; Cytokines - biosynthesis; Drug Synergism; Epidermal growth factor; Extracellular Matrix - physiology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene expression; Humans; Immunopathology; inflammation; interstitial extracellular matrix; Kinases; Medical sciences; Muscular system; Myocytes, Smooth Muscle - drug effects; Proteins; Rodents; Signal Transduction; Smooth muscle; Studies; synthetic function; Trachea - cytology; Trachea - drug effects; β 2-adrenergic receptor agonists
• ISSN: 0091-6749; 1097-6825; 1365-2567
• DOI: 10.1016/j.jaci.2004.04.041

Human airway smooth muscle (ASM) has several properties and functions that contribute to asthma pathogenesis, and increasing attention is being paid to its synthetic capabilities. ASM can promote the formation of the interstitial extracellular matrix, and in this respect, ASM from asthmatic subjects compared with normal subjects responds differently, both qualitatively and quantitatively. Thus, ASM cells are important regulating cells that potentially contribute to the known alterations within the extracellular matrix in asthma. In addition, through integrin-directed signaling, extracellular matrix components can alter the proliferative, survival, and cytoskeletal synthetic function of ASM cells. ASM also functions as a rich source of biologically active chemokines and cytokines that are capable of perpetuating airway inflammation in asthma and chronic obstructive pulmonary disease by promoting recruitment, activation, and trafficking of inflammatory cells in the airway milieu. Emerging evidence shows that airway remodeling may also be a result of the autocrine action of secreted inflammatory mediators, including T H2 cytokines, growth factors, and COX-2–dependent prostanoids. Finally, ASM cells contain both β 2-adrenergic receptors and glucocorticoid receptors and may represent a key target for β 2-adrenergic receptor agonist/corticosteroid interactions. Combinations of long-acting β 2-agonists and corticosteroids appear to have additive and/or synergistic effects in inhibiting inflammatory mediator release and the migration and proliferation of ASM cells.