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The role of high‐mobility group box‐1 ( HMGB 1) in the pathogenesis of asthma
Author(s) -
Shim E.J.,
Chun E.,
Lee H.S.,
Bang B.R.,
Kim T.W.,
Cho S.H.,
Min K.U.,
Park H.W.
Publication year - 2012
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/j.1365-2222.2012.03998.x
Subject(s) - hmgb1 , asthma , pathogenesis , immunology , medicine , sputum , eosinophil , inflammation , bronchoalveolar lavage , eosinophilia , rage (emotion) , eotaxin , lung , pathology , biology , tuberculosis , neuroscience
Summary Background High‐mobility group box 1 protein ( HMGB 1) belonging to endogenous danger signals prolongs eosinophil survival and acts as a chemoattractant.Objective The authors evaluated the role of HMGB 1 in the pathogenesis of asthma characterized by eosinophilic airway inflammation.Methods Firstly, HMGB 1 expressions in induced sputum obtained from human asthmatics were determined. This was followed by an evaluation of the role of HMGB 1 in a murine model of asthma using anti‐ HMGB 1 antibodies. Then the effect of HMGB 1 on the receptor of advanced glycation end products ( RAGE ) expressions on CD 11b‐ CD 11c + cells isolated from a murine model of asthma were measured to elucidate the mechanisms involved.Results Sputum HMGB 1 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, HMGB 1 expressions in lung tissue and HMGB 1 levels in bronchoalveolar lavage fluid were significantly elevated and eosinophilic airway inflammation, non‐specific airway hyperresponsiveness, and pathological changes were attenuated by blocking HMGB 1 activity. Furthermore, we found that enhanced RAGE expressions on CD 11b‐ CD 11c + also significantly decreased when HMGB 1 activity was blocked.Conclusion and Clinical Relevance Our findings suggest that HMGB 1 plays a key role in the pathogenesis of clinical and experimental asthma characterized by eosinophilic airway inflammation.