The Effects Of Interleukin-17and Suppressor Of Cytokine Signaling3in The Mice Of Neutrophilic Asthma

Part Ⅰ Exploration of a mice model of neutrophilic asthmaObjective To establish a mice model of neutrophilic asthma with different doses of lipopolysaccharide on a mice model of allergic asthma.Methods80BALB/c mice were randomly divided into four groups: group A (control group), group B (lung injury groups:B1～B4), group C (eosinophilic asthma group), group D (neutrophilic asthma groups:D1～D4). They were divided into sensitized and stimulated phase, sensitized phase:group A:intra-peritoneal injection with PBS and nasal drip with PBS, group B: intra-peritoneal injection with PBS and nasal drip with LPS (lipopolysaccharides), group C:intra-peritoneal injection with OVA(ovalbumin); stimulated phase:group A and B:atomization with saline,group C and D: atomization with5%OVA. Physiologic responses to atomization and change of lung tissue were observed; Total cell counts and classification in BALF (bronchoalveolar lavage fluid) were measured; OVA-specific IgE levels in serum were detected for evaluating the establishment of the model.Results (1) The mice of group D3presented fast breathing, urinary and fecal incontinence.(2) The total cell counts of BALF in group D3were significantly higher than that of group A (P<0.01). The percentage of neutrophils of group D3was significantly higher than that of group A, C, D1and D2(P<0.01, respectively). The percentage of eosinophils of group D3was significantly higher than that of group A, but lower than that of group C (P<0.01, respectively).(3) The airway wall thickening, partial ruptured,and more neutrophils infiltration in the airway mucosa and submucosa were seen in lung pathology of group D3.(4) The level of OVA-sIgE in serum of group D3was significantly higher than that of group A, but lower than that of group C (P<0.05, respectively).(5) The level of IL-4in BALF of group D3was significantly higher than that of group A, but IFN-y was lower than that of group A (P<0.05, respectively), but there were no significant differences between group D3and group C (P>0.05, respectively).Conclusion A mice model of NA could be successfully established with intranasal applications of10μg LPS+intraperitoneal injection of50μg OVA sensibilized three times and with5%OVA aerosol inhalation challenged for two weeks. Part II The effects of Interleukin-17and Suppressor of Cytokine Signaling3on the mice of neutrophilic asthmaObjective To explore the effects of Interleukin-17and Suppressor of Cytokine Signaling3on the mice of neutrophilic asthma.Methods NC group (normal control group), EA group (eosinophilic asthma group), NA group (neutrophilic asthma group) were established as previously described. The level of IL-17in BALF and the expression of SOCS3in lung were detected, investigating the effects of Interleukin-17and Suppressor of Cytokine Signaling3in the mice of neutrophilic asthma.Results (1) The mice of EA and NA group presented fast breathing, urinary and fecal incontinence.(2) The airway wall thickening, partial ruptured in lung pathology of EA and NA group, and more NEU infiltration in the airway mucosa and submucosa were seen in NA group but more EOS in EA group.(3) The total cell number of BALF in EA and NA group were significantly higher than that of NC group (P<0.01, respectively); EOS%of EA group was significantly higher than that of NC and NA group (P<0.01, respectively); NEU%of NA group was significantly higher than that of NC and EA group(P<0.01, respectively).(4) The level of OVA-sIgE in serum in NA group was significantly higher than that of NC group but lower than EA group (P<0.05, respectively).(5) The level of IL-17of BALF in NA group was significantly higher than that of NC and EA group(P<0.01, respectively); and there was a strong correlation (rs=0.583, P<0.05) between the level of IL-17and NEU%in BALF.(6) The expression of SOCS3in lung of EA and NA group was significantly higher than that of NC group, it was distributed in the airway epithelial cells, inflammatory cells’cytoplasm in EA group, however, distributed in the airway epithelial cells’cytoplasm in NA group.(7) The expression of SOCS3was not detected in the lung of all groups by WB.Conclusion The level of IL-17in BALF increased in NA group, and there was a strong correlation between the level of IL-17and NEU%in BALF, IL-17may play a role in neutrophilic airway inflammation of NA mice...