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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2004-8-6
pubmed:abstractText
Glutaredoxins (Grx) are thiol-disulfide oxidoreductases with antioxidant capacity and catalytic functions closely associated with glutathione, an antioxidant abundantly present in human lung. The present study investigated the expression of both human glutaredoxins in cultured human lung cells and lung homogenates by reverse-transcription polymerase chain reaction and Western blotting. Immunohistochemical studies were conducted with 38 human lung specimens, including healthy lung, parenchymal sarcoidosis, extrinsic allergic alveolitis, and usual interstitial pneumonia (UIP). The ultrastructural localization of Grx1 was assessed by immunoelectron microscopy. In addition, cultured airway epithelial cells were exposed to tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta. Both Grx1 and Grx2 could be detected at the mRNA and protein level in cultured human lung cells, but only Grx1 was prominently expressed in lung homogenates and alveolar macrophages. Immunohistochemically, Grx1 was highly concentrated to alveolar macrophages and weakly positive in the bronchial epithelium. Grx1 was ultrastructurally localized to the plasma membrane, cytoplasmic vacuoles, and nucleus. The expression of Grx1 decreased in alveolar macrophages of sarcoidosis and allergic alveolitis compared with the case for controls (P < 0.001), and bronchial epithelium of these diseases revealed no Grx1 immunoreactivity. Fibroblast foci and other fibrotic areas in UIP were mainly negative. In A549 cells, Grx1 was down-regulated by TGF-beta, whereas TNF-alpha caused no clear effect. Overall, high expression of Grx1 in alveolar macrophages suggests its importance in the primary defense of human lung. Decreased expression of Grx1 further suggests the impairment of this system both in inflammatory and fibrotic lung diseases, consistent with the down-regulation of Grx1 by TGF-beta in vitro.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0046-8177
pubmed:author
pubmed:issnType
Print
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1000-7
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:15297967-Blotting, Western, pubmed-meshheading:15297967-Cell Line, Transformed, pubmed-meshheading:15297967-Epithelial Cells, pubmed-meshheading:15297967-Female, pubmed-meshheading:15297967-Fluorescent Antibody Technique, Indirect, pubmed-meshheading:15297967-Glutaredoxins, pubmed-meshheading:15297967-Humans, pubmed-meshheading:15297967-Lung, pubmed-meshheading:15297967-Lung Diseases, Interstitial, pubmed-meshheading:15297967-Macrophages, Alveolar, pubmed-meshheading:15297967-Male, pubmed-meshheading:15297967-Microscopy, Immunoelectron, pubmed-meshheading:15297967-Middle Aged, pubmed-meshheading:15297967-Oxidoreductases, pubmed-meshheading:15297967-RNA, Messenger, pubmed-meshheading:15297967-Respiratory Mucosa, pubmed-meshheading:15297967-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:15297967-Transforming Growth Factor beta, pubmed-meshheading:15297967-Tumor Necrosis Factor-alpha
pubmed:year
2004
pubmed:articleTitle
Expression of glutaredoxin is highly cell specific in human lung and is decreased by transforming growth factor-beta in vitro and in interstitial lung diseases in vivo.
pubmed:affiliation
Department of Internal Medicine, University of Oulu, Finland.
pubmed:publicationType
Journal Article