Vestigated the effect of H89 in mouse models of asthma Seve

Vestigated the effect of H89 in mouse models of asthma. Several models of allergic asthma have been developed in mice. Although these models promote a T helper type 2 cell biased pulmonary inflammation, apparent disparities exist reflecting differences in the strains of mice examined and/or in the protocols used for antigen sensitization and challenge. For these reasons, we decided to assess the anti-inflammatory properties of H89 using two models of allergic asthma and two commonly used strains of mice. The acute model we used consisted of sensitization of Balb/c mice by intraperitoneal injection of chicken egg ovalbumin adsorbed on the MEDChem Express Astragalus polysaccharide adjuvant aluminum hydroxide, followed by repetitive intranasal challenges with OVA. The use of alum promotes a strong eosinophilic inflammation in the lung, and airway hyperresponsiveness that are however independent of IgE production, B cells or mast cells. The moderate model we used in C57BL/6 mice consisted of sensitization with OVA in the absence of adjuvant, followed by challenges with OVA. Although we did not observe the development of any significant AHR in these conditions, adjuvant-free models of asthma reproduce several features of human asthma including the inflammatory infiltrate and are fully dependent on mast cells when performed in mice on the Th1-prone C57BL/6 background but not in mice on the Th2-prone Balb/c background. We show that H89 is a potent inhibitor of AHR associated with the acute asthma model. Lung inflammation, mucus production and infiltration of eosinophils were reduced by treatment with H89 in both asthma models. Interestingly, treatment with H89 totally inhibited macrophage 956104-40-8 recruitment in BAL fluid in the moderate model without any effect on infiltrated macrophages in the acute model, suggesting their mode of activation is different. We also observed low but significant numbers of neutrophils and lymphocytes in BAL fluid, whose recruitment was also blocked by H89 in both models. These anti-inflammatory properties of H89 most likely occurred through suppression of Th2 cytokine production as demonstrated here for IL-4 and IL-5 measured in BAL fluid, which is in agreement with findings reporting that H89 can inhibit IL-5 promoter activity and IL-5 production by Th2 cells in vitro. Treatment