TY - JOUR
T1 - Soluble guanylyl cyclase expression is reduced in allergic asthma
AU - Papapetropoulos, Andreas
AU - Simoes, Davina C.M.
AU - Xanthou, Georgia
AU - Roussos, Charis
AU - Gratziou, Christina
PY - 2006/1
Y1 - 2006/1
N2 - Soluble guanylyl cyclase (sGC) is an enzyme highly expressed in the lung that generates cGMP contributing to airway smooth muscle relaxation. To determine whether the bronchoconstriction observed in asthma is accompanied by changes in sGC expression, we used a well-established murine model of allergic asthma. Histological and biochemical analyses confirmed the presence of inflammation in the lungs of mice sensitized and challenged with ovalbumin (OVA). Moreover, mice sensitized and challenged with OVA exhibited airway hyperreactivity to methacholine inhalation. Steady-state mRNA levels for all sGC subunits (α1, α2, and β1) were reduced in the lungs of mice with allergic asthma by 60-80%, as estimated by real-time PCR. These changes in mRNA were paralleled by changes at the protein level: α1, α2, and β1 expression was reduced by 50-80% as determined by Western blotting. Reduced α1 and β1 expression in bronchial smooth muscle cells was demonstrated by immunohistochemistry. To study if sGC inhibition mimics the airway hyperreactivity seen in asthma, we treated naïve mice with a selective sGC inhibitor. Indeed, in mice receiving ODQ the methacholine dose response was shifted to the left. We conclude that sGC expression is reduced in experimental asthma contributing to the observed airway hyperreactivity.
AB - Soluble guanylyl cyclase (sGC) is an enzyme highly expressed in the lung that generates cGMP contributing to airway smooth muscle relaxation. To determine whether the bronchoconstriction observed in asthma is accompanied by changes in sGC expression, we used a well-established murine model of allergic asthma. Histological and biochemical analyses confirmed the presence of inflammation in the lungs of mice sensitized and challenged with ovalbumin (OVA). Moreover, mice sensitized and challenged with OVA exhibited airway hyperreactivity to methacholine inhalation. Steady-state mRNA levels for all sGC subunits (α1, α2, and β1) were reduced in the lungs of mice with allergic asthma by 60-80%, as estimated by real-time PCR. These changes in mRNA were paralleled by changes at the protein level: α1, α2, and β1 expression was reduced by 50-80% as determined by Western blotting. Reduced α1 and β1 expression in bronchial smooth muscle cells was demonstrated by immunohistochemistry. To study if sGC inhibition mimics the airway hyperreactivity seen in asthma, we treated naïve mice with a selective sGC inhibitor. Indeed, in mice receiving ODQ the methacholine dose response was shifted to the left. We conclude that sGC expression is reduced in experimental asthma contributing to the observed airway hyperreactivity.
KW - Bronchoconstriction
KW - Guanosine 3′,5′-cyclic monophosphate, airway hyperreactivity
KW - Nitric oxide
UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-33644805991&partnerID=MN8TOARS
U2 - 10.1152/ajplung.00330.2005
DO - 10.1152/ajplung.00330.2005
M3 - Article
C2 - 16143586
AN - SCOPUS:33644805991
SN - 1040-0605
VL - 290
SP - L179-L184
JO - American Journal of Physiology - Lung Cellular and Molecular Physiology
JF - American Journal of Physiology - Lung Cellular and Molecular Physiology
IS - 1
ER -