| TGF-{beta}2 reduces nitric oxide synthase mRNA through a ROCK-dependent pathway in airway epithelial cells. | |
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MedLine Citation:
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PMID: 21685242 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Exhaled nitric oxide (eNO) is a potential non-invasive biomarker of inflammation in asthma. The significant intersubject variability of eNO within clinically similar patients has contributed to its limited clinical application. Arginase and NO synthase (NOS) utilize the same substrate (L-arginine), and contribute to the fibrotic and inflammatory features of asthma, respectively. Interestingly, TGF-β2 can increase the expression of arginase, stimulates fibrosis, and is overexpressed in asthma. We hypothesized that TGF-β2-enhanced arginase activity would decrease gas phase NO release from lung epithelial cells by limiting L-arginine availability for NOS. Our results show that TGF-β2 (5 ng/ml) significantly enhances total arginase activity up to 2-3 fold in both primary small airway epithelial cells (SAECs) and the A549 cell line. Preincubation with TGF-β2 prior to cytokine (IL-1β, TNF-α, and IFN-γ, 10 ng/mL each) stimulation decreases gas phase NO release to baseline levels (from 1.66 ± 0.52 to 0.30 ± 0.12 pl.s(-1).cm(-2) and from 0.27 ± 0.03 pl.s(-1).cm(-2) to near zero in SAEC and A549 cells, respectively). Addition of arginase inhibitor (nor-NOHA) or siRNA only partly reverses the reduction. In contrast, Rho-kinase (ROCK) pathway inhibitor (Y-27632) completely recovers the cytokine-induced NO flux in the present of TGF-β2. iNOS mRNA and protein levels change in a similar trend as NO release from the cells. We conclude that TGF-β2 impacts cytokine-induced NO production in airway epithelial cells by reducing iNOS mRNA and protein levels through a ROCK-dependent pathway. |
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Authors:
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Jingjing Jiang; Steven C George |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-6-17 |
Journal Detail:
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Title: American journal of physiology. Lung cellular and molecular physiology Volume: - ISSN: 1522-1504 ISO Abbreviation: - Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-6-20 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901229 Medline TA: Am J Physiol Lung Cell Mol Physiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1University of California, Irvine. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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