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Estrogen reduces AHR, stimulates NO release and inhibits ROS production in murine asthmatic airways
Author(s) -
Dimitropoulou Christiana,
Intapad Suttira,
Snead Connie,
Wiseman Dean A,
Black Stephen M,
Catravas John D
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.622.11
Subject(s) - nitric oxide , ovalbumin , ovariectomized rat , endocrinology , sensitization , medicine , chemistry , estrogen , superoxide , immunology , immune system , biochemistry , enzyme
We have reported that estrogen (E2) reduces inflammation and airway hyper‐responsiveness (AHR) in a murine model of allergic asthma. To study the underlying mechanisms, female BALB/c ovariectomized mice were implanted with sc pellets releasing either vehicle or E2 and subjected to a 25‐day regimen of ovalbumin (OVA) sensitization. Acute (30min) exposure of tracheal rings isolated from vehicle‐treated, OVA‐sensitized mice (asthmatic) to 100nM E2 reduced the constrictor effects of carbachol. Western blot analysis revealed increased pNOS/NOS ratio in asthmatic lung homogenates exposed to E2 (100nM) for 30min, compared to vehicle‐exposed homogenates. Similarly, in tracheal smooth muscle cells harvested from asthmatic mice (SMC), nitric oxide (NO) production increased after 30min exposure to E2 (100nM); this was reversed by the NOS1 inhibitor 7‐NINA. 30min E2 exposure reduced superoxide production in SMC. To investigate the chronic effects of E2, Rac1 and p47phox expression was analyzed by Western blotting in lung homogenates from asthmatic mice treated with vehicle or E2. E2‐treated asthmatic mice exhibited lower lung expression of both Rac1 and p47phox, suggesting inhibition of NAD(P)H oxidase. These data suggest that E2, acutely or chronically, inhibits AHR, stimulates NOS1 activation and NO release and reduces NAD(P)H oxidase function and superoxide production in a mouse model of allergic asthma.