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

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.