Aims: This study determines whether KMUP-1 inhalation suppresses ovalbumine (OVA)-sensitized and -
challenged peri-bronchial vascular inflammation and remodeling in mice.
Methods and Results: After short-term KMUP-1 (1-5 mM, 30 min)-nebulization and L-NAME (12 mM, 15 min)-
pretreatment, endothelial nitric oxide synthase (eNOS) and matrix metalloproteinases-9 (MMP-9) expression in lung were
measured by Western blotting analysis. In 28-days experiment, mice were sensitized with intraperitoneal OVA on day 1
and day 8, challenged with OVA nebulization and treated with KMUP-1 nebulization (5 mM, 30 mins) on day 21-27.
Expression of eNOS, inducible nitric oxide synthase (iNOS), soluble guanylyl cyclase (sGC), protein kinase G (PKG),
MMP-9, VCAM-1 and ICAM-1 were measured by Western blotting analysis. eNOS- and MMP-9-immunostaining were
used for peri-vascular or peri-bronchial localization. Hematoxylin and eosin staining was used to show the vascular and
bronchial wall thickness and infiltration of inflammatory cells. Cell counting and measurement of NOmetabolite (NOx) in
bronchoalveolar lavage fluid (BALF) were used to examine the NO production. KMUP-1 increased eNOS and decreased
MMP-9 expression. L-NAME-pretreatment reversed these changes. KMUP-1 reduced OVA-sensitized vascular and
bronchial wall thickening, eNOS-immunostaining at the alveolar septa, MMP-9-immunostaining in the bronchioles and
infiltrated inflammatory cells in the peri-vascular and peri-bronchiolar regions. The OVA-sensitized decrease of sGC and
PKG and increase of iNOS, ICAM-1/VCAM-1 and plasma cytokines IL-5/IL-13 were reversed; cell count, NOx and
MMP-9-activity in BALF were decreased by KMUP-1.
Conclusions: Inhaled KMUP-1, preventing allergic pulmonary vascular inflammation and remodeling, would be useful for
the treatment of asthma and respiratory obstruction disease.