Document Detail


Nitric oxide synthase enzymes in the airways of mice exposed to ovalbumin: NOS2 expression is NOS3 dependent.
MedLine Citation:
PMID:  20953358     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES AND DESIGN: The function of the airway nitric oxide synthase (NOS) isoforms and the lung cell types responsible for its production are not fully understood. We hypothesized that NO homeostasis in the airway is important to control inflammation, which requires upregulation, of NOS2 protein expression by an NOS3-dependent mechanism.
MATERIALS OR SUBJECTS: Mice from a C57BL/6 wild-type, NOS1(-/-), NOS2(-/-), and NOS3(-/-) genotypes were used. All mice strains were systemically sensitized and exposed to filtered air or ovalbumin (OVA) aerosol for two weeks to create a subchronic model of allergen-induced airway inflammation.
METHODS: We measured lung function, lung lavage inflammatory and airway epithelial goblet cell count, exhaled NO, nitrate and nitrite concentration, and airway NOS1, NOS2, and NOS3 protein content.
RESULTS: Deletion of NOS1 or NOS3 increases NOS2 protein present in the airway epithelium and smooth muscle of air-exposed animals. Exposure to allergen significantly reduced the expression of NOS2 protein in the airway epithelium and smooth muscle of the NOS3(-/-) strain only. This reduction in NOS2 expression was not due to the replacement of epithelial cells with goblet cells as remaining epithelial cells did not express NOS2. NOS1(-/-) animals had significantly reduced goblet cell metaplasia compared to C57Bl/6 wt, NOS2(-/-), and NOS3(-/-) allergen-exposed mice.
CONCLUSION: The airway epithelial and smooth muscle cells maintain a stable airway NO concentration under noninflammatory conditions. This "homeostatic" mechanism is unable to distinguish between NOS derived from the different constitutive NOS isoforms. NOS3 is essential for the expression of NOS2 under inflammatory conditions, while NOS1 expression contributes to allergen-induced goblet cell metaplasia.
Authors:
Jennifer M Bratt; Keisha Williams; Michelle F Rabowsky; Michael S Last; Lisa M Franzi; Jerold A Last; Nicholas J Kenyon
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-10-05
Journal Detail:
Title:  Mediators of inflammation     Volume:  2010     ISSN:  1466-1861     ISO Abbreviation:  Mediators Inflamm.     Publication Date:  2010  
Date Detail:
Created Date:  2010-10-18     Completed Date:  2011-02-02     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  9209001     Medline TA:  Mediators Inflamm     Country:  United States    
Other Details:
Languages:  eng     Pagination:  -     Citation Subset:  IM    
Affiliation:
Pulmonary and Critical Care Medicine, School of Medicine, Genome and Biomedical Sciences Facility, University of California, Davis, CA 95616, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Gene Deletion
Gene Expression Regulation, Enzymologic*
Goblet Cells / cytology
Inflammation
Lung / pathology
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Nitric Oxide Synthase Type I / genetics*
Nitric Oxide Synthase Type II / genetics*
Nitric Oxide Synthase Type III / genetics*
Ovalbumin / chemistry*
Protein Isoforms
Grant Support
ID/Acronym/Agency:
ES-05707/ES/NIEHS NIH HHS; KO8 HL-076415/HL/NHLBI NIH HHS; T32 ES-07059/ES/NIEHS NIH HHS; T32 HL-07013/HL/NHLBI NIH HHS; TW-05718/TW/FIC NIH HHS; UL1RR02416/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Protein Isoforms; 9006-59-1/Ovalbumin; EC 1.14.13.39/Nitric Oxide Synthase Type I; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 1.14.13.39/Nos1 protein, mouse; EC 1.14.13.39/Nos2 protein, mouse; EC 1.14.13.39/Nos3 protein, mouse
Comments/Corrections

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