Effects of 1,25(OH)2D3 on airway inflammation and expression of HMGB1 and MMP-9 in lung tissue of asthmatic mice
Objective:To observe the changes of 1,25(OH)2D3 on airway inflammation and high mobility group B1(HMGB1),matrix metalloproteinase-9(MMP-9)mRNA and protein expression in asthmatic mice.Methods:Thirty-six C57BL/6 female mice were randomly divided into 3 groups:control group(Control),asthma group(PBS/asthma),and 1,25(OH)2D3 intervention asthma group(1,25(OH)2D3/asthma),with 12 mice in each group.The asthmatic mice model was established by the hypersensitivity and atomization inhalation of the ovalbumin mixture.The 1,25(OH)2D3 group was injected with 1,25(OH)2D3(4 μg/kg)mixture before each stimulation,and the control group and the asthma group were injected with PBS.Hematoxylin eosin(HE)staining and periodic acid Schiffs staining(PAS)was adopted to detect the degree of inflammatory cell infiltration and the hyperplasia of bronchial goblet cells respectively.After bronchoalveolar lavage fluid(BALF)centrifugation,Th2 cy-tokines(IL-4,IL-5,IL-13)and Th17 cytokine(IL-17A)in the supernatant were detected by ELISA.The content of serum total immunoglobulin E(total IgE)and OVA-specific immunoglobulin E(OVA-IgE)in serum were also detected by ELISA.Results:The lung tissue inflammation scores and basal membrane circumference standardized PAS+goblet cell area(APAS+/Pbm)of mice in the 1,25(OH)2D3 intervention group were lower or less than those in the asthma group(P<0.05).The expression levels of Th2 cytokines(IL-4,IL-5,IL-13),Th17 cytokine(IL-17A),HMGB1,MMP-9 in BALF and total IgE and OVA-IgE in the asthma group were higher than those in the control group(P<0.05),while those in the 1,25(OH)2D3 intervention group(1,25(OH)2D3/asthma)were significantly lower than those in the asthma group(P<0.05).The expression levels of HMGB1 and MMP-9 pro-teins and mRNA in the lung tissue of the control group mice were lower,while their expression levels in the lung tissue of the asthma group mice were significantly higher.However,the expression levels of HMGB1 and MMP-9 proteins and mRNA in the lung tissue of the 1,25(OH)2D3 intervention group(1,25(OH)2D3/asthma)mice were wholly lower than those in the asthma group(P<0.05).Conclu-sion:A moderate amount of 1,25(OH)2D3 can reduce airway inflammation in asthmatic mice.The possible mechanism of preventing airway inflammation in asthmatic mice is by inhibiting the expres-sion of HMGB1 and MMP-9.
1,25-Dihydroxyvitamin D3AsthmaHigh Mobility Group B1Matrix Metallo-proteinase-9
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