Role of Airway Smooth Muscle in Asthma: Contraction and Beyond

Abstract

Asthma is a chronic inflammatory disease characterized by reversible airway obstruction, airway hyperresponsiveness, and airway inflammation. Airway smooth muscle (ASM), existing in the trachea and in the bronchial tree up to the terminal bronchioles, serves as an important structural effector tissue to regulate bronchomotor tone. However, the physiological relevance of ASM in healthy lungs is still unclear. In a disease status such as asthma, the role of ASM has been conventionally thought of as a passive tissue regulating bronchomotor tone. Nevertheless, growing evidence shows that ASM may also be involved in the development of airway inflammation and airway remodeling. The contraction of ASM regulates the airway luminal diameter and modulates airway resistance, which can be augmented by cytokines as well as extracellular matrix alterations leading to airway hyperresponsiveness. ASM may also serve as an immunomodulatory cell, regulating airway inflammation. In addition, ASM mass increases in asthma and may represent a proliferative response due to chronic inflammation. This evidence suggests that ASM undergoes marked phenotypic modulation in a disease status such as asthma. This review will present evidence that ASM, a passive contractile tissue, may also play an important role in the perpetuation of airway inflammation and the remodeling of the airway in asthma. Further investigation and understanding of the cellular and molecular mechanisms that regulate ASM functions may offer new therapeutic approaches in the treatment of asthma.