Expression of high-mobility group box 1 and of receptor for advanced glycation end products in chronic obstructive pulmonary disease
| Autor: | Gary P. Sims, Marie-Christine Dombret, Marielle Maret, Séverine Létuvé, Martine Grandsaigne, Michel Aubier, Marina Pretolani, Nassima Ferhani, Alexander Kozhich, Roland Kolbeck, Olivier Thibaudeau, Anthony J. Coyle |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Pulmonary and Respiratory Medicine
Male Interleukin-1beta Receptor for Advanced Glycation End Products Fluorescent Antibody Technique chemical and pharmacologic phenomena Bronchi Critical Care and Intensive Care Medicine HMGB1 Proinflammatory cytokine RAGE (receptor) Cell Line Pulmonary Disease Chronic Obstructive Intensive care Macrophages Alveolar medicine Humans HMGB1 Protein Receptors Immunologic Lung COPD medicine.diagnostic_test biology business.industry Respiratory disease Smoking Forced Expiratory Flow Rates respiratory system Middle Aged medicine.disease Immunohistochemistry respiratory tract diseases Bronchoalveolar lavage medicine.anatomical_structure Immunology biology.protein Airway Remodeling Female business Bronchoalveolar Lavage Fluid |
| Zdroj: | American journal of respiratory and critical care medicine. 181(9) |
| ISSN: | 1535-4970 |
| Popis: | Chronic obstructive pulmonary disease (COPD) is characterized by airway inflammation and remodeling. High-mobility group box 1 (HMGB1), a nuclear protein that is released during inflammation and repair, interacts with proinflammatory cytokines and with the receptor for advanced glycation end products (RAGE), which is highly expressed in the lung.To determine whether HMGB1 is augmented in COPD and is associated with IL-1beta and RAGE.HMGB1 was assessed in the bronchoalveolar lavage (BAL) of 20 never-smokers, 20 smokers, and 30 smokers with COPD and it was correlated with inflammatory and clinical parameters. In parallel, HMGB1 and RAGE immunolocalization was determined in bronchial and lung tissues. Last, binding of HMGB1 to IL-1beta in human macrophages and in BAL fluid was examined.BAL levels of HMGB1 were higher in smokers with COPD than in smokers and never-smokers (P0.0001 for both comparisons), and similar differences were observed in epithelial cells and alveolar macrophages. BAL HMGB1 correlated positively with IL-1beta (r(s) = 0.438; P = 0.0006) and negatively with FEV(1) (r(s) = -0.570; P0.0001) and transfer factor of the lung for carbon monoxide (r(s) = -0.382; P = 0.0026). HMGB1-IL-1beta complexes were found in BAL supernatant and alveolar macrophages from smokers and patients with COPD, as well as in the human macrophage cell line, THP-1, where they enhanced the synthesis of tumor-necrosis factor-alpha. RAGE was overexpressed in the airway epithelium and smooth muscle of patients with COPD and it colocalized with HMGB1.Elevated HMGB1 expression in COPD airways may sustain inflammation and remodeling through its interaction with IL-1beta and RAGE. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|