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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.
MedLine Citation:
PMID:  22452605     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 intra-peritoneal OVA on day 1 and day 8, challenged with OVA nebulization and treatedwith 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 NO metabolite (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 region. 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.
Authors:
Chung-Pin Liu; Chung-Han Hsieh; Bin-Nan Wu; Jwu-Lai Yeh; Zen-Kong Dai; Chee-Yin Chai; Ing-Jun Chen
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-28
Journal Detail:
Title:  Inflammation & allergy drug targets     Volume:  -     ISSN:  2212-4055     ISO Abbreviation:  Inflamm Allergy Drug Targets     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-3-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101266886     Medline TA:  Inflamm Allergy Drug Targets     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Pharmacology, Faculty of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung 807, Taiwan. ingjun@kmu.edu.tw.
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