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Expression of high-mobility group box 1 and of receptor for advanced glycation end products in chronic obstructive pulmonary disease.
Am J Respir Crit Care Med. 2010 May 01; 181(9):917-27.AJ

Abstract

RATIONALE

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.

OBJECTIVES

To determine whether HMGB1 is augmented in COPD and is associated with IL-1beta and RAGE.

METHODS

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.

MEASUREMENTS AND MAIN RESULTS

BAL levels of HMGB1 were higher in smokers with COPD than in smokers and never-smokers (P < 0.0001 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; P < 0.0001) 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.

CONCLUSIONS

Elevated HMGB1 expression in COPD airways may sustain inflammation and remodeling through its interaction with IL-1beta and RAGE.

Authors+Show Affiliations

Institut National de la Santé et de la Recherche Médicale (INSERM) U700, Physiopathologie et Epidémiologie de l'Insuffisance Respiratoire, Paris, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20133931

Citation

Ferhani, Nassima, et al. "Expression of High-mobility Group Box 1 and of Receptor for Advanced Glycation End Products in Chronic Obstructive Pulmonary Disease." American Journal of Respiratory and Critical Care Medicine, vol. 181, no. 9, 2010, pp. 917-27.
Ferhani N, Letuve S, Kozhich A, et al. Expression of high-mobility group box 1 and of receptor for advanced glycation end products in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2010;181(9):917-27.
Ferhani, N., Letuve, S., Kozhich, A., Thibaudeau, O., Grandsaigne, M., Maret, M., Dombret, M. C., Sims, G. P., Kolbeck, R., Coyle, A. J., Aubier, M., & Pretolani, M. (2010). Expression of high-mobility group box 1 and of receptor for advanced glycation end products in chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine, 181(9), 917-27. https://doi.org/10.1164/rccm.200903-0340OC
Ferhani N, et al. Expression of High-mobility Group Box 1 and of Receptor for Advanced Glycation End Products in Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2010 May 1;181(9):917-27. PubMed PMID: 20133931.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Expression of high-mobility group box 1 and of receptor for advanced glycation end products in chronic obstructive pulmonary disease. AU - Ferhani,Nassima, AU - Letuve,Séverine, AU - Kozhich,Alexander, AU - Thibaudeau,Olivier, AU - Grandsaigne,Martine, AU - Maret,Marielle, AU - Dombret,Marie-Christine, AU - Sims,Gary P, AU - Kolbeck,Roland, AU - Coyle,Anthony J, AU - Aubier,Michel, AU - Pretolani,Marina, Y1 - 2010/02/04/ PY - 2010/2/6/entrez PY - 2010/2/6/pubmed PY - 2010/5/15/medline SP - 917 EP - 27 JF - American journal of respiratory and critical care medicine JO - Am J Respir Crit Care Med VL - 181 IS - 9 N2 - RATIONALE: 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. OBJECTIVES: To determine whether HMGB1 is augmented in COPD and is associated with IL-1beta and RAGE. METHODS: 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. MEASUREMENTS AND MAIN RESULTS: BAL levels of HMGB1 were higher in smokers with COPD than in smokers and never-smokers (P < 0.0001 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; P < 0.0001) 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. CONCLUSIONS: Elevated HMGB1 expression in COPD airways may sustain inflammation and remodeling through its interaction with IL-1beta and RAGE. SN - 1535-4970 UR - https://www.unboundmedicine.com/medline/citation/20133931/Expression_of_high_mobility_group_box_1_and_of_receptor_for_advanced_glycation_end_products_in_chronic_obstructive_pulmonary_disease_ L2 - https://www.atsjournals.org/doi/10.1164/rccm.200903-0340OC?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -