S100A12 and the Airway Smooth Muscle: Beyond Inflammation and Constriction

Abstract

Airway inflammation, lung remodeling, and Airway Hyperresponsiveness (AHR) are major features of asthma and Chronic Obstructive Pulmonary Disease (COPD). The inflammatory response to allergens, air pollutants, and other insults is likely to play a key role in promoting structural changes in the lung including the overabundance of Airway Smooth Muscle (ASM) seen in asthmatics. These alterations or remodeling could, in turn, impact the immunmodulatory actions of the ASM, the ASM's contractile properties, and the development of AHR. New evidences suggest that airway inflammation and AHR are not tightly related to each other and that the structural component of the airway, mainly the ASM, is a chief driver of AHR. Members of the S100/calgranulins family have been implicated in the regulation of inflammation and cell apoptosis in various systems. S100A12 is highly expressed in neutrophils and is one of the most abundant proteins in the lungs of patients with asthma or COPD. Studies with genetic engineered mice with smooth muscle cell-targeted expression of human S100A12 revealed that S100A12 reduces airway smooth muscle amounts and dampens airway inflammation and airway hyperreactivity in a model of allergic lung inflammation. Thus, targeting airway smooth muscle for instance through delivery of pro-apoptotic S100A12 could represent an attractive means to promote ASM apoptosis and to reduce ASM abundance in asthmatics.