CC16: A link between airway infection and obstructive lung disease.
Asthma and COPD are the most commonly diagnosed chronic lung diseases in the United States. While it is now recognized that a percentage of severe asthmatics develop fixed airway obstruction, little known pertaining to the basic underlying mechanisms of this progression. This proposal will examine the role of club cell secreted protein (CC16) in the context of airway infection as a previously overlooked link in understanding this progression. Our preliminary data provides strong supportive evidence that CC16 is an important mediator during M. pneumoniae infection. However, these findings may be immediately applicable to other pulmonary pathogens. Since CC16 is an established biomarker, our studies may provide a novel therapeutic approach for treating individuals with low circulating CC16 in order to prevent lung function decline over time.
Surfactant Protein-A regulation of eosinophil apoptosis in asthma.
Asthma is a chronic disease of the airways characterized by inflammation and obstruction. This proposal investigates the mechanism by which surfactant protein-A (SP-A) regulates eosinophil apoptosis, a previously unrecognized protective role of SP-A in asthma. By mediating eosinophil apoptosis, SP-A limits the accumulation and release of cytotoxic mediators associated with eosinophils, which can exacerbate asthma severity. Understanding how SP-A regulates inflammation will help us develop novel strategies to treat asthma.
Surfactant Protein-A as a novel therapeutic for asthma.
Asthma is a chronic disease of the airways characterized by inflammation and obstruction and affects approximately 10% of the US population. This proposal will evaluate an innovative treatment for asthma that involves a 10-amino acid peptide sequence that is derived from the active site of an endogenous lung protein, surfactant protein-A, using human lung cell lines and mouse models. Our preliminary data suggest that this peptide attenuates phenotypes associated with asthma, including inflammatory cell recruitment, mucin production and airway hyper-responsiveness. Optimization of the SP-A peptide may yield a new class of therapy for asthma sufferers.