Abstract��OBJECTIVE To study the effect of celastrol on the airway inflammation and Th17 cells in obese asthmatic mice.METHODS Thirty male C57BL/6 mices were randomly divided into five groups sham group, ovalbumin(OVA)+DMSO group, diet-induced obesity(DIO)+DMSO group, DIO+OVA+DMSO group, DIO+OVA+celastrol group. H&E staining was used to examine histological changes in the lungs. Immunohistochemistry was used to observe IL-17A protein in lung tissues; flow cytometry was used to detect the proportion of Th17 cells in CD4+T cells. The expression of IL-17A mRNA in lung was examined by quantitative real-time RT-PCR, while concentration of cytokines IL-17A in serum was assessed by standardized sandwich ELISA. RESULTS OVA+DMSO group and DIO+OVA+DMSO group showed significant higher inflammatory cells infiltration in the airways and small perivascular spaces of the lungs compared with sham group. DIO+DMSO group showed less inflammatory cells infiltration than DIO+OVA+DMSO group. However, DIO+OVA+celastrol group showed significantly reduced inflammatory cells infiltration. The expression of IL-17A in lung tissues, IL-17A mRNA in mice lung and serum IL-17A level from DIO+OVA+DMSO group, OVA+DMSO group, and DIO+DMSO group significantly increased compared with sham group (P<0.01). However, the expression of IL-17A in lung tissues, IL-17A mRNA in mice lung and serum IL-17A level significantly decreased in DIO+OVA+celastrol group compared with DIO+OVA+DMSO group (P<0.01). A significant increase of Th17 cells in CD4+T cell of mice spleen was found in OVA+DMSO group, DIO+DMSO group and DIO+OVA+DMSO group compared with sham group (P<0.01). Though, DIO+OVA +celastrol group revealed a significant reduction of Th17 cells compared with DIO +OVA +DMSO group (P<0.01).CONCLUTION Celastrol administration downregulates Th17 cells, decreases IL-17A production in obese asthmatic mice. Celastrol effectively alleviates airway inflammation in obese asthatic mice.
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