Reactive oxygen and nitrogen intermediates increase transforming growth factor-beta1 release from human epithelial alveolar cells through two different mechanisms
| Autor: | Bruno Fouqueray, Antoine Flahault, Agnès Bellocq, Jacques Cadranel, Laurent Baud, Stefano Marullo, Elie Azoulay, Carole Philippe |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Transforming Growth Factor beta/*secretion
Time Factors Transcription Genetic medicine.medical_treatment Clinical Biochemistry Guanosine Monophosphate chemistry.chemical_compound Transforming Growth Factor beta Superoxide Dismutase/pharmacology Cycloheximide Enzyme Inhibitors RNA Processing Post-Transcriptional Enzyme Inhibitors/pharmacology Protein Synthesis Inhibitors Nitrogen/*pharmacology Free Radical Scavengers Epithelial Cells/metabolism medicine.anatomical_structure NG-Nitroarginine Methyl Ester Protein Synthesis Inhibitors/pharmacology Guanosine Monophosphate/physiology Atrial Natriuretic Factor Pulmonary and Respiratory Medicine Free Radical Scavengers/pharmacology medicine.medical_specialty Xanthine Oxidase Nitrogen Biology Arginine Cell Line Alveolar cells Superoxide dismutase Xanthine Oxidase/pharmacology Atrial Natriuretic Factor/pharmacology Internal medicine medicine Humans NG-Nitroarginine Methyl Ester/pharmacology Protein kinase A Xanthine oxidase Hydrogen Peroxide/metabolism Molecular Biology Cyclic guanosine monophosphate Dose-Response Relationship Drug Reactive Oxygen Species Superoxide Dismutase Growth factor Epithelial Cells Cell Biology Hydrogen Peroxide Pulmonary Alveoli/*drug effects/*physiology Molecular biology Pulmonary Alveoli Endocrinology chemistry biology.protein Cycloheximide/pharmacology Arginine/pharmacology Dichlororibofuranosylbenzimidazole/pharmacology Dichlororibofuranosylbenzimidazole Transforming growth factor |
| Zdroj: | American Journal of Respiratory Cell and Molecular Biology, Vol. 21, No 1 (1999) pp. 128-36 |
| ISSN: | 1044-1549 |
| Popis: | Transforming growth factor (TGF)- b 1 is a growth factor involved in the mechanisms of lung repair and fibrosis that follow inflammatory processes. We sought to examine the link between the generation of reactive oxygen intermediates (ROI) or reactive nitrogen intermediates (RNI) by inflammatory cells and the expression of TGF- b 1 by alveolar epithelial cells. Exposure of the A549 lung epithelial cell line to either an ROI generating system (xanthine and xanthine oxidase) or an RNI donor (S-nitroso- N -acetyl-penicillamine [SNAP]) promoted a time- and dose-dependent increase in TGF- b 1 release, as measured by a specific enzyme-linked immunosorbent assay. At the peak, the levels of TGF- b 1 were twice the control values. The induction of TGF- b 1 release by ROI was blunted by catalase and unaffected by superoxide dismutase, indicating the involvement of hydrogen peroxide. The response was also blunted by 5,6dichloro-1- b - D -ribofuranosyl benzimidazole (DRB), a specific RNA polymerase II inhibitor, and accompanied by a corresponding increase in TGF- b 1 messenger RNA, as measured by quantitative/competitive reverse transcription polymerase chain reaction, suggesting the involvement of transcriptional mechanisms and possibly other downstream mechanisms. In contrast, RNI-induced TGF- b 1 release was unaffected by DRB and blunted by the protein synthesis inhibitor cycloheximide, suggesting the involvement of translational and post-translational mechanisms. This response required cyclic guanosine monophosphate (cGMP)‐ mediated processes because ( 1 ) immunoreactive cGMP accumulated in the culture medium of SNAPtreated cells; ( 2 ) SNAP-induced TGF- b 1 release was blunted by KT 5823, an inhibitor of cGMP-dependent protein kinase; and ( 3 ) similar increase in TGF- b 1 release was obtained by cell exposure to membrane-permeable dibutyryl-cGMP or to atrial natriuretic factor, a known agonist of particulate guanylate cyclase. These data suggest that in vitro exposure of human alveolar epithelial cells to ROI and RNI enhances TGF- b 1 release through different mechanisms. In vivo , this control may constitute a molecular link between inflammatory and fibrotic processes. Bellocq, A., E. Azoulay, S. Marullo, A. Flahault, B. Fouqueray, C. Philippe, J. Cadranel, and L. Baud. 1999. Reactive oxygen and nitrogen intermediates increase transforming growth factor‐ b 1 release from human epithelial alveolar cells through two different mechanisms. Am. J. Respir. Cell Mol. Biol. 21:128‐136. |
| Databáze: | OpenAIRE |
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