Pulmonary endothelium as a site of synthesis and storage of interleukin-6 in experimental congestive heart failure
| Autor: | Antonino Nicoletti, Delphine Lepailleur-Enouf, Monique Philippe, Roger Gaertner, Walter Gonzalez, Chantal Mandet, Jean-Jacques Mercadier, Jean-Baptiste Michel |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Male
medicine.medical_specialty Endothelium Pleural effusion Blotting Western Down-Regulation Hemodynamics Ventricular Dysfunction Left Antigens CD Internal medicine medicine.artery Cytokine Receptor gp130 medicine Animals Humans Myocardial infarction Rats Wistar Heart Failure Aorta Membrane Glycoproteins Lung Interleukin-6 Reverse Transcriptase Polymerase Chain Reaction business.industry NF-kappa B Pulmonary edema medicine.disease Rats Up-Regulation medicine.anatomical_structure Heart failure cardiovascular system Cardiology Endothelium Vascular Cardiology and Cardiovascular Medicine business |
| Zdroj: | European Journal of Heart Failure. 5:435-442 |
| ISSN: | 1388-9842 |
| DOI: | 10.1016/s1388-9842(03)00002-3 |
| Popis: | Background: Pulmonary endothelium is an early upstream hemodynamic target of left ventricular dysfunction. Interleukin 6 (IL-6) is a pro-inflammatory cytokine reported to increase in congestive heart failure (CHF) patients. Aims: We sought to determine the origin of IL-6, IL-6 receptor (IL-6R) and gp130 in experimental CHF. Methods: We used rats with coronary artery ligation as an experimental model of either compensated or decompensated heart failure. Lung and aorta samples were analysed by RT-PCR, ELISA and immunohistochemistry for IL-6 and its receptors. Results: IL-6 mRNA expression increased in the lung of rats with decompensated heart failure and was positively correlated with infarct severity whereas IL-6R mRNA decreased in the lung of myocardial infarction rats and gp130 mRNA remained unchanged. In contrast, there were no changes in IL-6 mRNA expression in the aorta and left ventricular myocardium. IL-6 peptide content as determined by ELISA and Western Blot in lung tissue was 2-fold higher in decompensated heart failure as compared to control rats. These data were confirmed by immunohistochemistry showing a preferential endothelial localization of IL-6 in the CHF lung. IL-6 peptide was also present in the pleural effusion of decompensated heart failure and was positively correlated with IL-6 mRNA expression in the lungs of decompensated HF rats. Pulmonary IL-6 overexpression was associated with nuclear translocation of NF-κB and cytosolic degradation of IκB. Conclusion: Dysfunctional pulmonary endothelium is a source of synthesis and storage of IL-6 in an experimental model of CHF. |
| Databáze: | OpenAIRE |
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