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Clin Exp Allergy. 2012 Jun;42(6):958-65. doi: 10.1111/j.1365-2222.2012.03998.x.

The role of high-mobility group box-1 (HMGB1) in the pathogenesis of asthma.

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1
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.

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.

[Indexed for MEDLINE]

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