Determining the Role of Brain-Type Creatine Kinase in the Lungs During Asthma

Abstract

Creatine kinase (CK) is an enzyme that regulates cellular energy homeostasis by catalyzing the reversible transfer of high energy phosphates from ATP to creatine, forming phosphocreatine as part of the creatine-phosphocreatine energy shuttle. Brain-type creatine kinase (CKB) is the predominant isoenzyme in normal human lung tissue and has been identified by our collaborators as a potential biomarker for asthma. Using a mouse house dust mite (HDM) model of asthma and cultured human respiratory cells, this project investigates the role of CKB in the context of asthma. We show that CKB expression is initially downregulated during HDM challenge, but is significantly upregulated during resolution. Inhibition of CKB during the resolution phase in a mouse model resulted in persistence of airway hyperresponsiveness and mucus presence in the airways. These results suggest that CKB may play a protective role in the lungs, potentially in mucociliary clearance during resolution, which could aid in restoring normal pulmonary function in the context of asthma.