Synthetic responses in airway smooth muscle

J Allergy Clin Immunol. 2004 Aug;114(2 Suppl):S32-50. doi: 10.1016/j.jaci.2004.04.041.

Abstract

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(H)2 cytokines, growth factors, and COX-2-dependent prostanoids. Finally, ASM cells contain both beta(2)-adrenergic receptors and glucocorticoid receptors and may represent a key target for beta(2)-adrenergic receptor agonist/corticosteroid interactions. Combinations of long-acting beta(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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Adrenal Cortex Hormones / pharmacology
  • Adrenergic beta-2 Receptor Agonists
  • Adrenergic beta-Agonists / pharmacology
  • Animals
  • Asthma / etiology
  • Bronchi / cytology
  • Bronchi / drug effects*
  • Chemokines / biosynthesis
  • Cytokines / biosynthesis
  • Drug Synergism
  • Extracellular Matrix / physiology
  • Humans
  • Myocytes, Smooth Muscle / drug effects*
  • Signal Transduction
  • Trachea / cytology
  • Trachea / drug effects*

Substances

  • Adrenal Cortex Hormones
  • Adrenergic beta-2 Receptor Agonists
  • Adrenergic beta-Agonists
  • Chemokines
  • Cytokines