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Sputum HMGB1 expressions were markedly higher in asthmatics than in normal controls, and were selleck chemicals llc positively correlated with sputum eosinophilia and sputum TNF-��, 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. Our findings suggest that HMGB1 plays a key role in the pathogenesis of clinical and experimental asthma characterized by eosinophilic airway inflammation. ""Background Local allergic rhinitis (LAR) is characterized by in situ production of specific IgE (sIgE) antibodies and a positive response to a nasal allergen provocation test (NAPT) in the absence of atopy. Objective The aim of this study was to investigate the immunological mechanisms involved in the immediate and late responses after nasal exposure to Dermatophagoides pteronyssinus (DP) in patients with LAR. Methods A total of 40 subjects with LAR to DP were studied and compared with 50 healthy controls. Immediate and late responses to NAPT-DP were assessed using a visual analogue scale of nasal symptoms and acoustic rhinometry. Tryptase, ECP, total and sIgE-DP were measured S1PR1 in the nasal lavage by immunoassay at baseline, 15?min, 1, 6 and 24?h after nasal challenge. Results NAPT-DP was positive in all patients, with significant increases in tryptase (45%), ECP (65%) and sIgE-DP (25%) (Pcheck details response to NAPT-DP and 40% a dual response. Immediate responders showed a fast release of tryptase with a peak at 15?min after NAPT-DP, and a progressive increase in nasal ECP and sIgE-DP from 1 to 24?h after challenge, with a peak at 24?h. Dual responders presented persistently higher levels of tryptase from 15?min to 6?h after challenge, and a similar pattern of nasal release of ECP and sIgE-DP to immediate responders. There were no isolated late responders. NAPT-DP was negative in all healthy controls, with no increases in tryptase, ECP, or total and sIgE-DP in nasal secretions. Conclusions The results demonstrated the existence of immediate and dual responses to a NAPT with DP in LAR patients, with the local presence of sIgE and mast cell/eosinophil activation. Cite this as: S. L��pez, C. Rond��n, M. J. Torres, P. Campo, G. Canto, R. Fernandez, R. Garcia, A. Mart��nez-Ca?avate and M. Blanca, Clinical & Experimental Allergy, 2010 (40) 1007�C1014. ""Effective allergy immunotherapy (IT) requires patient compliance.