Activation of hypoxia-inducible factor-1alpha via nuclear factor-kappa B in rats with chronic obstructive pulmonary disease
| Autor: | Hong Jiang, Ye-sen Zhu, Qifang Li, Hui Xu, Yu Sun |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Lipopolysaccharides
Male Vascular Endothelial Growth Factor A Pyrrolidines Immunoblotting Biophysics Administration Oral Pharmacology Biochemistry Antioxidants Pulmonary function testing Rats Sprague-Dawley chemistry.chemical_compound Pulmonary Disease Chronic Obstructive Pyrrolidine dithiocarbamate Thiocarbamates Smoke Tobacco medicine Animals Lung COPD medicine.diagnostic_test business.industry Reverse Transcriptase Polymerase Chain Reaction NF-kappa B General Medicine Hypoxia (medical) medicine.disease Hypoxia-Inducible Factor 1 alpha Subunit respiratory tract diseases Rats Respiratory Function Tests Vascular endothelial growth factor Vascular endothelial growth factor A Bronchoalveolar lavage chemistry Hypoxia-inducible factors Immunology Cytokines medicine.symptom Blood Gas Analysis business Bronchoalveolar Lavage Fluid Heme Oxygenase-1 |
| Zdroj: | Acta biochimica et biophysica Sinica. 42(7) |
| ISSN: | 1745-7270 |
| Popis: | Accumulating data suggested that hypoxia inducible factor (HIF)-1alpha plays an important role in the evolution and propagation of the inflammatory process. To characterize the activation of HIF-1alpha in rats with chronic obstructive pulmonary disease (COPD) and examine the possible role of nuclear factor (NF)-kappaB in this process, rats were challenged by introtracheal instillation of lipopolysaccharide (LPS) and exposure to cigarette smoke. Pyrrolidine dithiocarbamate (PDTC) was administered via the oral route 1 h before LPS or cigarettes administration. Four weeks later, pulmonary function and histology were tested; bronchoalveolar lavage fluid (BALF) and arterial blood gases were assayed. Activation of pulmonary NF-kappaB was assessed by quantitative PCR, immunoblot analysis, and electrophoretic mobility shift assay, respectively. Results showed that LPS and smog induced the characteristics of COPD seen in human. PDTC alleviated the development of COPD and the levels of cytokines in BALF of PDTC+COPD group were significantly decreased compared with that of COPD group. The activation of pulmonary NF-kappaB was inhibited by PDTC and the accumulation of HIF-1alpha gene expression in the COPD group was attenuated by PDTC pretreatment. Furthermore, the mRNA levels of HIF-1alpha target genes heme oxygenase-1 (HO-1) and vascular endothelial growth factor (VEGF) were parallel to the attenuation of HIF-1alpha by PDTC. These findings indicated that the activation of HIF-1alpha pathway via NF-kappaB contributes to the development of COPD, and administration of NF-kappaB inhibitor may attenuate the development of COPD. |
| Databáze: | OpenAIRE |
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