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Respiratory Research
Published in: Respiratory Research 1/2010

Open Access 01-12-2010 | Research

The cationic amino acid transporter 2 is induced in inflammatory lung models and regulates lung fibrosis

Authors: Kathryn A Niese, Monica G Chiaramonte, Lesley G Ellies, Marc E Rothenberg, Nives Zimmermann

Published in: Respiratory Research | Issue 1/2010

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Abstract

Background

Arginine is an amino acid that serves as a substrate for the enzymes nitric oxide synthase (NOS) and arginase, leading to synthesis of NO and ornithine, respectively. As such, arginine has the potential to influence diverse fundamental processes in the lung.

Methods

We used mice deficient in cationic amino acid transporter (CAT) 2 in models of allergic airway inflammation and pulmonary fibrosis.

Results

We report that the arginine transport protein CAT2 was over-expressed in the lung during the induction of allergic airway inflammation. Furthermore, CAT2 mRNA was strongly induced by transgenically over-expressed IL-4, and allergen-induced expression was dependent upon signal-transducer-and-activator-of-transcription (STAT) 6. In situ mRNA hybridization demonstrated marked staining of CAT2, predominantly in scattered mononuclear cells. Analysis of allergic airway inflammation and bleomycin-induced inflammation in CAT2-deficient mice revealed that while inflammation was independent of CAT2 expression, bleomycin-induced fibrosis was dependent upon CAT2. Mechanistic analysis revealed that arginase activity in macrophages was partly dependent on CAT2.

Conclusion

Taken together, these results identify CAT2 as a regulator of fibrotic responses in the lung.
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Metadata
Title
The cationic amino acid transporter 2 is induced in inflammatory lung models and regulates lung fibrosis
Authors
Kathryn A Niese
Monica G Chiaramonte
Lesley G Ellies
Marc E Rothenberg
Nives Zimmermann
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2010
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/1465-9921-11-87

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