Apoptosis-Regulatory Factors as Potential Drug Targets in the Epithelium of Normal and Inflamed Airways

P.   D.   Zalewski; R.   E.   Ruffin

Abstract

Airway epithelium (AE) lines the conducting airways of the respiratory system and functions to maintain airway integrity by providing both a physical barrier to inhaled noxious agents and a mechanism for their clearance via the mucociliary escalator. Normal AE cells are relatively refractory to a number of apoptotic stimuli and survival mechanisms are in place to maintain the integrity of the epithelial barrier that is exposed to agents such as reactive oxygen species (ROS) and death receptor ligands secreted by immune cells during inflammation. When damage to AE does occur, there is increased AE apoptosis, such as in the airway damage that occurs in the chronically inflamed airways in diseases like asthma where rates of AE apoptosis can be increased many-fold. The usual treatment for persistent asthma in humans involves a combination of bronchodilator and inhaled corticosteroid; there is however a need to develop strategies to better control other aspects of the disease, including minimizing the ongoing damage to AE and consequent airway remodeling. Targeting of the major apoptosis-regulatory factors in AE may be one such strategy. Here we review what is known about apoptosis and its regulatory factors in normal AE and abnormalities in these factors in the inflamed airways of mice and humans.

Keywords: Airway epithelium, Apoptosis, Necrosis, Airway damage, Inflammation, Asthma, Caspases, Therapy