tailieunhanh - Báo cáo y học: " The cationic amino acid transporter 2 is induced in inflammatory lung models and regulates lung fibrosis"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học 'Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: " The cationic amino acid transporter 2 is induced in inflammatory lung models and regulates lung fibrosis. | Niese et al. Respiratory Research 2010 11 87 http content 11 1 87 RESPIRATORY RESEARCH RESEARCH Open Access The cationic amino acid transporter 2 is induced in inflammatory lung models and regulates lung fibrosis Kathryn A Niese 1 Monica G Chiaramonte2 Lesley G Ellies3 Marc E Rothenberg1 4 and Nives Zimmermann 1 4 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. Background Recent studies have implicated amino acids specifically tryptophan and arginine in the regulation of immunity and tolerance. Elegant studies demonstrated an important role for tryptophan metabolism through indoleam-ine 2 3-dioxygenase IDO in inhibition of experimental asthma 1 . However the role of arginine transport and metabolism remains unclear. Intracellular .

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