tetra(4-n-methylpyridyl)porphine and Asthma

Oxidative stress is important in the pathogenesis of allergic asthma. Extracellular superoxide dismutase (EC-SOD; SOD3) is the major antioxidant in lungs, but its role in allergic asthma is unknown. Here we report that asthmatics have increased SOD3 transcript levels in sputum and that a single nucleotide polymorphism (SNP) in SOD3 (R213G; rs1799895) changes lung distribution of EC-SOD, and decreases likelihood of asthma-related symptoms. Knockin mice analogous to the human R213G SNP had lower airway hyperresponsiveness, inflammation, and mucus hypersecretion with decreased interleukin-33 (IL-33) in bronchoalveolar lavage fluid and reduced type II innate lymphoid cells (ILC2s) in lungs. SOD mimetic (Mn (III) tetrakis (N-ethylpyridinium-2-yl) porphyrin) attenuated Alternaria-induced expression of IL-33 and IL-8 release in BEAS-2B cells. These results suggest that R213G SNP potentially benefits its carriers by resulting in high EC-SOD in airway-lining fluid, which ameliorates allergic airway inflammation by dampening the innate immune response, including IL-33/ST2-mediated changes in ILC2s.

Topics: Aged; Animals; Asthma; Bronchoalveolar Lavage Fluid; Cell Line; Cohort Studies; Cytokines; Female; Genotype; Humans; Hypersensitivity; Immunity, Innate; Interleukin-33; Lymphocytes; Male; Mice; Mice, Transgenic; Middle Aged; Ovalbumin; Phenotype; Polymorphism, Single Nucleotide; Porphyrins; Respiratory Hypersensitivity; RNA, Messenger; Sputum; Superoxide Dismutase