101. Expression of glutaredoxin is highly cell specific in human lung and is decreased by transforming growth factor-β in vitro and in interstitial lung diseases in vivo
- Author
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Vuokko L. Kinnula, Paavo Pääkkö, Marjaana Säily, Mirva J Peltoniemi, Ylermi Soini, Raija Sormunen, Riitta Kaarteenaho-Wiik, and Arne Holmgren
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Immunoelectron microscopy ,Blotting, Western ,Extrinsic Allergic Alveolitis ,Respiratory Mucosa ,Biology ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Transforming Growth Factor beta ,Usual interstitial pneumonia ,Glutaredoxin ,Macrophages, Alveolar ,medicine ,Humans ,RNA, Messenger ,Fluorescent Antibody Technique, Indirect ,Microscopy, Immunoelectron ,Lung ,Glutaredoxins ,Cell Line, Transformed ,030304 developmental biology ,0303 health sciences ,medicine.diagnostic_test ,Reverse Transcriptase Polymerase Chain Reaction ,Tumor Necrosis Factor-alpha ,Epithelial Cells ,Middle Aged ,respiratory system ,medicine.disease ,respiratory tract diseases ,3. Good health ,Bronchoalveolar lavage ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Female ,Tumor necrosis factor alpha ,Lung Diseases, Interstitial ,Oxidoreductases ,Transforming growth factor - Abstract
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 (P0.001), 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.
- Published
- 2004