Role of Airway Smooth Muscle in Inflammation Related to Asthma and COPD.

Airway smooth muscle contributes to both contractility and inflammation in the pathophysiology of asthma and COPD. Airway smooth muscle cells can change the degree of a variety of functions, including contraction, proliferation, migration, and the secretion of inflammatory mediators (phenotype plasticity). Airflow limitation, airway hyperresponsiveness, β-adrenergic desensitization, and airway remodeling, which are fundamental characteristic features of these diseases, are caused by phenotype changes in airway smooth muscle cells. Alterations between contractile and hyper-contractile, synthetic/proliferative phenotypes result from Ca dynamics and Ca sensitization. Modulation of Ca dynamics through the large-conductance Ca-activated K channel/L-type voltage-dependent Ca channel linkage and of Ca sensitization through the RhoA/Rho-kinase pathway contributes not only to alterations in the contractile phenotype involved in airflow limitation, airway hyperresponsiveness, and β-adrenergic desensitization but also to alteration of the synthetic/proliferative phenotype involved in airway remodeling. These Ca signal pathways are also associated with synergistic effects due to allosteric modulation between β-adrenergic agonists and muscarinic antagonists. Therefore, airway smooth muscle may be a target tissue in the therapy for these diseases. Moreover, the phenotype changing in airway smooth muscle cells with focuses on Ca signaling may provide novel strategies for research and development of effective remedies against both bronchoconstriction and inflammation.