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

• Published in: Respiratory research Vol. 11; no. 1; p. 87
• Main Authors: Niese, Kathryn A, Chiaramonte, Monica G, Ellies, Lesley G, Rothenberg, Marc E, Zimmermann, Nives
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 24.06.2010; BioMed Central; BMC
• Subjects: Allergens; Allergy; Amino Acid Transport Systems, Basic - deficiency; Amino Acid Transport Systems, Basic - genetics; Amino Acid Transport Systems, Basic - metabolism; Animals; Arginase - metabolism; Arginine; Arginine - metabolism; Asthma; Asthma - chemically induced; Asthma - genetics; Asthma - immunology; Asthma - metabolism; Bleomycin; Carrier proteins; Children & youth; Cloning; Collagen; Collagen - metabolism; Cytokines - metabolism; Disease Models, Animal; Enzymes; Fibrosis; Health aspects; Homeostasis; Hospitals; Inflammation; Inflammation Mediators - metabolism; Interleukin-4 - genetics; Interleukin-4 - metabolism; Lung - immunology; Lung - metabolism; Macrophages - enzymology; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Nitric oxide; Ovalbumin; Polyamines; Pulmonary fibrosis; Pulmonary Fibrosis - chemically induced; Pulmonary Fibrosis - genetics; Pulmonary Fibrosis - immunology; Pulmonary Fibrosis - metabolism; Respiratory tract diseases; Risk factors; RNA; RNA polymerase; RNA, Messenger - metabolism; STAT6 Transcription Factor - deficiency; STAT6 Transcription Factor - genetics; Studies; Up-Regulation; United States
• ISSN: 1465-993X; 1465-9921; 1465-993X; 1465-9921
• DOI: 10.1186/1465-9921-11-87

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. We used mice deficient in cationic amino acid transporter (CAT) 2 in models of allergic airway inflammation and pulmonary fibrosis. 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. Taken together, these results identify CAT2 as a regulator of fibrotic responses in the lung.