The R213G polymorphism in SOD3 protects against allergic airway inflammation
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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The R213G polymorphism in SOD3 protects against allergic airway inflammation. / Gaurav, Rohit; Varasteh, Jason T; Weaver, Michael R; Jacobson, Sean R; Hernandez-Lagunas, Laura; Liu, Qing; Nozik-Grayck, Eva; Chu, Hong Wei; Alam, Rafeul; Nordestgaard, Børge G; Kobylecki, Camilla J; Afzal, Shoaib; Chupp, Geoffrey L; Bowler, Russell P.
I: JCI insight, Bind 2, Nr. 17, e95072, 2017.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - The R213G polymorphism in SOD3 protects against allergic airway inflammation
AU - Gaurav, Rohit
AU - Varasteh, Jason T
AU - Weaver, Michael R
AU - Jacobson, Sean R
AU - Hernandez-Lagunas, Laura
AU - Liu, Qing
AU - Nozik-Grayck, Eva
AU - Chu, Hong Wei
AU - Alam, Rafeul
AU - Nordestgaard, Børge G
AU - Kobylecki, Camilla J
AU - Afzal, Shoaib
AU - Chupp, Geoffrey L
AU - Bowler, Russell P
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1172/jci.insight.95072
DO - 10.1172/jci.insight.95072
M3 - Journal article
C2 - 28878123
VL - 2
JO - JCI Insight
JF - JCI Insight
SN - 2379-3708
IS - 17
M1 - e95072
ER -
ID: 185685027