Abstract
BackgroundAirway inflammation and asthma have been linked to oxidative stress and the melastatin-related transient receptor potential cation channel, member 2 (TRPM2), which can be activated by reactive oxygen species (ROS), has emerged as a potential therapeutic target for inflammatory diseases.ObjectiveUsing TRPM2 deficient (TRPM2-/-) mice, we investigated whether the TRPM2 ion channel, which mediates calcium (Ca2+) influx and lysosomal Ca2+ release, plays a role in the pathophysiology of severe allergic asthma in mouse.MethodsSevere allergic asthma was initiated in wild type (WT) and TRPM2-/- mice by repeated sensitization with ovalbumin (OVA)/aluminum hydroxide on Days 0, 7 and 14, followed by intranasal challenge on Days 21, 22 and 23. Mice were investigated for the presence of airway responsiveness, airway inflammation, production of allergen-specific antibodies, cytokine response and lung pathology.ResultsThe absence of TRPM2 channels has no obvious effect on major etiologic markers of severe allergic asthma in this mouse model. Neither airway resistance nor mucus production are affected in TRPM2-/- mice. TRPM2 channel ablation also does not alter airway inflammation or immunocyte infiltration and does not affect antibody response or cytokine levels.ConclusionsTRPM2 is not required for airway inflammation in OVA-induced severe allergic asthma in mice. Accordingly, TRPM2 might not be a suitable therapeutic target for airway inflammation caused by allergens in humans.
Highlights
Airway inflammation and asthma have been linked to oxidative stress and the melastatin-related transient receptor potential cation channel, member 2 (TRPM2), which can be activated by reactive oxygen species (ROS), has emerged as a potential therapeutic target for inflammatory diseases
We found that airway responsiveness, airway inflammation, production of allergenspecific antibodies, and cytokine response were unaffected in TRPM2-/- mice when compared to OVA-sensitized and challenged wild type (WT) mice
Airway resistance and mucus production are not affected in TRPM2-/- mice Given that airway inflammation and asthma have been linked to oxidative stress [2], we investigated whether TRPM2, a Ca2+-permeable ion channel involved in ROS signaling, contributes to pathophysiology
Summary
Airway inflammation and asthma have been linked to oxidative stress and the melastatin-related transient receptor potential cation channel, member 2 (TRPM2), which can be activated by reactive oxygen species (ROS), has emerged as a potential therapeutic target for inflammatory diseases. Objective: Using TRPM2 deficient (TRPM2-/-) mice, we investigated whether the TRPM2 ion channel, which mediates calcium (Ca2+) influx and lysosomal Ca2+ release, plays a role in the pathophysiology of severe allergic asthma in mouse. Asthma is a chronic airway inflammation characterized by intense eosinophil, mast cell, and lymphocyte infiltration, mucus hyper-production, and airway hyper-responsiveness [1]. Activated phagocytic cells (neutrophils, eosinophils, monocytes and macrophages) play a role in the pathophysiology of airway inflammation due their release of large amounts of reactive oxygen species (ROS), lipid mediators, and cytokines [2,3]. It has been suggested that ROS play a role in airway disorders such as adult respiratory, distress syndrome (ARDS), cystic fibrosis, idiopathic fibrosis, chronic obstructive pulmonary diseases (COPD), and asthma [3,5]
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