| Asymmetric dimethylarginine potentiates lung inflammation in a mouse model of allergic asthma. | |
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MedLine Citation:
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PMID: 20889675 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Nitric oxide (NO), formed by nitric oxide synthase (NOS), is an important mediator of lung inflammation in allergic asthma. Asymmetric dimethylarginine (ADMA), a competitive endogenous inhibitor of NOS, is metabolized by the enzyme dimethylarginine dimethylaminohydrolase (DDAH). Elevated ADMA has been shown to affect lung function in mice, and by inhibiting NOS it alters NO and reactive oxygen species production in mouse lung epithelial cells. However, the effects of altered ADMA levels during lung inflammation have not been explored. A model of allergen-induced airway inflammation was utilized in combination with the modulation of endogenous circulating ADMA levels in mice. Airway inflammation was assessed by quantifying inflammatory cell infiltrates in lung lavage and by histology. Lung DDAH expression was assessed by quantitative PCR and immunohistochemistry. Nitrite levels were determined in lung lavage fluid as a measure of NO production. iNOS expression was determined by immunohistochemistry, immunofluorescence, Western blot, and quantitative PCR. NF-κB binding activity was assessed by a transcription factor binding assay. Allergen-induced lung inflammation was potentiated in mice with elevated circulating ADMA and was reduced in mice overexpressing DDAH. Elevated ADMA reduced nitrite levels in lung lavage fluid in both allergen-challenged and control animals. ADMA increased iNOS expression in airway epithelial cells in vivo following allergen challenge and in vitro in stimulated mouse lung epithelial cells. ADMA also increased NF-κB binding activity in airway epithelial cells in vitro. These data support that ADMA may play a role in inflammatory airway diseases such as asthma through modulation of iNOS expression in lung epithelial cells. |
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Authors:
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Elizabeth Klein; Jason Weigel; Mary C Buford; Andrij Holian; Sandra M Wells |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-10-01 |
Journal Detail:
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Title: American journal of physiology. Lung cellular and molecular physiology Volume: 299 ISSN: 1522-1504 ISO Abbreviation: Am. J. Physiol. Lung Cell Mol. Physiol. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-06 Completed Date: 2011-01-13 Revised Date: 2011-12-21 |
Medline Journal Info:
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Nlm Unique ID: 100901229 Medline TA: Am J Physiol Lung Cell Mol Physiol Country: United States |
Other Details:
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Languages: eng Pagination: L816-25 Citation Subset: IM |
Affiliation:
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Dept. of Environmental, Agricultural, and Occupational Health, Univ. of Nebraska, Omaha, 68198-5910, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amidohydrolases
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genetics,
metabolism Animals Arginine / analogs & derivatives*, pharmacology Asthma* / chemically induced, immunology, pathology Bronchoalveolar Lavage Fluid / chemistry Disease Models, Animal* Enzyme Inhibitors / pharmacology* Epithelial Cells / cytology, drug effects, metabolism Humans Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Transgenic Nitric Oxide Synthase Type II / genetics, metabolism Nitrites / metabolism Ovalbumin / pharmacology Pneumonia* / chemically induced, immunology, pathology Respiratory Mucosa / cytology |
| Grant Support | |
ID/Acronym/Agency:
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K99-HL-088550/HL/NHLBI NIH HHS; P20-RR-017670/RR/NCRR NIH HHS; R00-HL-088550/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Nitrites; 30315-93-6/N,N-dimethylarginine; 74-79-3/Arginine; 9006-59-1/Ovalbumin; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.14.13.39/Nos2 protein, mouse; EC 3.5.-/Amidohydrolases; EC 3.5.3.18/dimethylargininase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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