Title |
The R213G polymorphism in SOD3 protects against allergic airway inflammation
|
---|---|
Published in |
JCI Insight, September 2017
|
DOI | 10.1172/jci.insight.95072 |
Pubmed ID | |
Authors |
Rohit Gaurav, Jason T. Varasteh, Michael R. Weaver, Sean R. Jacobson, Laura Hernandez-Lagunas, Qing Liu, Eva Nozik-Grayck, Hong Wei Chu, Rafeul Alam, Børge G. Nordestgaard, Camilla J. Kobylecki, Shoaib Afzal, Geoffrey L. Chupp, Russell P. Bowler |
Abstract |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 17 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Master | 3 | 18% |
Student > Doctoral Student | 2 | 12% |
Student > Ph. D. Student | 2 | 12% |
Professor | 2 | 12% |
Researcher | 1 | 6% |
Other | 1 | 6% |
Unknown | 6 | 35% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 7 | 41% |
Agricultural and Biological Sciences | 2 | 12% |
Biochemistry, Genetics and Molecular Biology | 1 | 6% |
Immunology and Microbiology | 1 | 6% |
Environmental Science | 1 | 6% |
Other | 0 | 0% |
Unknown | 5 | 29% |