Cytokines induce airway smooth muscle cell hyperresponsiveness to contractile agonists.
The important pathophysiological features of the airways in asthma include exaggerated narrowing to bronchoconstrictor agonists and attenuated relaxation to beta adrenoceptor stimulation. These physiological perturbations are associated with inflammation and remodelling of the airways, the latter including an increase in airway smooth muscle cell mass, disruption of the airway epithelium, and changes in the airway tissue extracellular matrix. Recent evidence suggests that cytokines, important molecules modulating airway inflammation, also directly decrease airway smooth muscle responsiveness to beta adrenergic agents, stimulate cytokine secretion, inhibit or promote airway smooth muscle proliferation, and "prime" airway smooth muscle to become hyperresponsive to bronchoconstrictors. Characterisation of the cellular and biochemical events that are involved in activation of airway smooth muscle is likely to be the major consideration in the design of future therapies for asthma. Because calcium is an essential regulatory element for cell growth and cell contraction, it is likely that alterations in calcium mobilisation may, in part, play a role in creating an airway smooth muscle phenotype that is hyperresponsive to contractile agonists. Further studies will be required to determine the precise mechanisms involved in cytokine modulation of calcium homeostasis in airway smooth muscle.
Amrani
Y
Y
Pulmonary and Critical Care Division, Hospital of the University of Pennsylvania, Philadelphia 19104-4283, USA.
Panettieri
R A
RA
D001249:Asthma / Q000378:metabolism; D001980:Bronchi / Q000378:metabolism*; D016085:Bronchoconstrictor Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D016207:Cytokines / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009130:Muscle, Smooth / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*
D016085:Bronchoconstrictor Agents; D016207:Cytokines; D019204:GTP-Binding Proteins; D002118:Calcium