The role of high-mobility group box-1 (HMGB1) in the pathogenesis of asthma.
Clin Exp Allergy
; 42(6): 958-65, 2012 Jun.
Article
en En
| MEDLINE
| ID: mdl-22909167
ABSTRACT
BACKGROUND:
High-mobility group box 1 protein (HMGB1) belonging to endogenous danger signals prolongs eosinophil survival and acts as a chemoattractant.OBJECTIVE:
The authors evaluated the role of HMGB1 in the pathogenesis of asthma characterized by eosinophilic airway inflammation.METHODS:
Firstly, HMGB1 expressions in induced sputum obtained from human asthmatics were determined. This was followed by an evaluation of the role of HMGB1 in a murine model of asthma using anti-HMGB1 antibodies. Then the effect of HMGB1 on the receptor of advanced glycation end products (RAGE) expressions on CD11b-CD11c(+) cells isolated from a murine model of asthma were measured to elucidate the mechanisms involved.RESULTS:
Sputum HMGB1 expressions were markedly higher in asthmatics than in normal controls, and were positively correlated with sputum eosinophilia and sputum TNF-α, IL-5 and IL-13 expressions. In a murine model of asthma, HMGB1 expressions in lung tissue and HMGB1 levels in bronchoalveolar lavage fluid were significantly elevated and eosinophilic airway inflammation, non-specific airway hyperresponsiveness, and pathological changes were attenuated by blocking HMGB1 activity. Furthermore, we found that enhanced RAGE expressions on CD11b-CD11c(+) also significantly decreased when HMGB1 activity was blocked. CONCLUSION AND CLINICAL RELEVANCE Our findings suggest that HMGB1 plays a key role in the pathogenesis of clinical and experimental asthma characterized by eosinophilic airway inflammation.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Asma
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Proteína HMGB1
Tipo de estudio:
Etiology_studies
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Prognostic_studies
Límite:
Adult
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Año:
2012
Tipo del documento:
Article