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.
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.
Authors: Elizabeth A Oczypok; Pavle S Milutinovic; John F Alcorn; Anupriya Khare; Lauren T Crum; Michelle L Manni; Michael W Epperly; Adriane M Pawluk; Anuradha Ray; Tim D Oury Journal: J Allergy Clin Immunol Date: 2015-04-28 Impact factor: 10.793
Authors: Mao Wang; Alex Gauthier; LeeAnne Daley; Katelyn Dial; Jiaqi Wu; Joanna Woo; Mosi Lin; Charles Ashby; Lin L Mantell Journal: Antioxid Redox Signal Date: 2019-07-11 Impact factor: 8.401