Grant: Operating Grant

Introduction: Asthma is a chronic disease characterized by inflammation and permanent changes in the airways and alveoli of the lungs, a process called remodeling. Many treatments have been tried to decrease inflammation with the goal of ameliorating asthma, but these have had limited benefit. Presumably, new treatments that could affect both immune cells and lung cells might be more successful. A family of enzymes called protein tyrosine phosphatases (PTP) regulates the production of soluble factors and other signals that affect inflammation. Because of this, an approach targeting PTP might be better than the current therapeutic strategies for asthma, which only affect only one cell type at a time. Hypothesis: The activity of PTP can be manipulated to control the inflammatory responses driven by immune cells and lung cells, and to prevent remodeling of the airways in chronic asthma. Objectives: My laboratory has found one PTP, called PTPRB, that can affect the way cells of the immune system and lung cells secrete soluble factors in an acute model of allergic airway inflammation that can be used to study asthma. Specific Aims: 1.To study the effect of decreasing the activity of PTPRB in a model of chronic allergic airway inflammation that resembles asthma. With these experiments, we want to understand the molecular mechanisms that are responsible for the altered production of soluble factors by cells of the immune system and lung cells. 2.To study the role of PTPRB in the relationship between inflammation and the development of lung remodeling. For these experiments, we will perform bone marrow transplantation between mice, to create combinations of immune cells and lung cells having different levels of PTPRB activity. Potential Impact: The discovery that PTPRB can ameliorate asthma could establish a new therapeutic approach, where a pharmacological PTP inhibitor drug could be used to decrease inflammation and lung damage at a young age.