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Inhaled KMUP-1 Prevents Allergic Pulmonary Vascular Inflammation and Remodeling via NO and Suppressed MMP-9 and ICAM-1/VCAM-1.
- Source :
-
Inflammation & allergy drug targets [Inflamm Allergy Drug Targets] 2012 Aug 01; Vol. 11 (4), pp. 251-61. - Publication Year :
- 2012
-
Abstract
- Aims: This study determines whether KMUP-1 inhalation suppresses ovalbumine (OVA)-sensitized and - challenged peri-bronchial vascular inflammation and remodeling in mice.<br />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.<br />Conclusions: Inhaled KMUP-1, preventing allergic pulmonary vascular inflammation and remodeling, would be useful for the treatment of asthma and respiratory obstruction disease.
- Subjects :
- Animals
Bronchi drug effects
Bronchi metabolism
Cyclic GMP-Dependent Protein Kinases metabolism
Female
Guanylate Cyclase metabolism
Hypersensitivity metabolism
Intercellular Adhesion Molecule-1 metabolism
Mice
Mice, Inbred BALB C
NG-Nitroarginine Methyl Ester pharmacology
Nitric Oxide Synthase Type II metabolism
Nitric Oxide Synthase Type III metabolism
Pneumonia metabolism
Pneumonia prevention & control
Receptors, Cytoplasmic and Nuclear metabolism
Soluble Guanylyl Cyclase
Vascular Cell Adhesion Molecule-1 metabolism
Airway Remodeling drug effects
Hypersensitivity drug therapy
Matrix Metalloproteinase 9 metabolism
Nitric Oxide metabolism
Piperidines administration & dosage
Pneumonia drug therapy
Xanthines administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 2212-4055
- Volume :
- 11
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Inflammation & allergy drug targets
- Publication Type :
- Academic Journal
- Accession number :
- 22452605
- Full Text :
- https://doi.org/10.2174/187152812800958960