Asthma is a chronic airway inflammation characterized by intense eosinophil, mast cell, and lymphocyte infiltration, mucus hyper-production, and airway hyper-responsiveness . Asthma symptoms develop when allergens activate antigen-specific helper T-lymphocytes (Th) to produce Th-2 cytokines, such as interleukin (IL)-4, IL-5, and IL13 . Activated phagocytic cells (neutrophils, eosinophils, monocytes and macrophages) also 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]. Airway cells and tissues are also exposed to oxidative stress elicited by environmental pollutants (ozone, cigarette smoke, and dust), infections, inflammatory reactions or decreased levels of antioxidants that lead to enhanced levels of ROS [3, 4]. It has been shown that ROS can damage DNA, lipids, proteins, and carbohydrates leading to impaired cellular functions and enhanced inflammatory reactions . Consequently, 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].
The mammalian super family of transient receptor potential (TRP) cation channels can be subdivided into six subfamilies based on sequence homology: TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPA (ankyrin), TRPP (polycystin) and TRPML (mucolipin) [6, 7]. TRP channels express in a broad range of cell types including sensory nerves, lung fibroblast, epithelial cells and immune cells [6, 7]. Relevant to the context of asthma, TRPA1 channels have been implicated in pain and inflammatory responses in the airways in mice . In addition, the TRPM2 channel has been implicated in stress-related inflammatory and neurodegenerative conditions [9–11]. However, the relevance of TRPM2 in severe asthma pathophysiology has not yet been explored.
TRPM2 is a non-selective calcium (Ca2+) influx and lysosomal Ca2+ release channel expressed in neutrophils [9, 12], monocytes , Jurkat T cells , INS-1 cells  and mouse bone marrow derived-dendritic cells (BMDC) . TRMP2 is co-activated by intracellular adenosine diphosphate ribose (ADPR) and Ca2+, downstream of ROS and chemokine signaling pathways [11, 15–17]. TRPM2 activation by ADPR is further facilitated by the presence of nicotinic acid adenine dinucleotide phosphate (NAADP), cyclic ADPR (cADPR), and hydrogen peroxide (H2O2) [18–21], whereas adenosine monophosphate (AMP) and permeating protons (pH) negatively regulate TRPM2 activation [21–24].
TRPM2-deficient mice are more resistant to chronic experimental colitis due to defective chemokine (C-X-C motif) ligand 2 (CXCL2) production by monocytes and reduced neutrophil infiltration . Yet, a recent publication has suggested no role for TRPM2 channel in chronic obstructive pulmonary disease . Intriguingly, cADPR induces Ca2+ release in airway smooth muscle (ASM) [26, 27] and acetylcholine (ACh) and endothelin-1 (ET-1) are considered to regulate airway caliber through cADPR-mediated Ca2+ release in these cells . Moreover, mice that lack CD38, an ectoenzyme that generates free ADPR through the hydrolysis of nicotinamide adenine dinucleotide (NAD+) and its cADPR glycohydrolase activity, exhibit altered airway responsiveness to methacholine [28, 29].
In the present study, we assessed the role of TRPM2 channels in airway inflammation by using an experimental OVA-induced severe asthma model. We found that airway responsiveness, airway inflammation, production of allergen-specific antibodies, and cytokine response were unaffected in TRPM2-/- mice when compared to OVA-sensitized and challenged WT mice. Our findings suggest that in this experimental model the TRPM2 channel is not required for airway inflammation to occur.