The role of SDF-1/CXCR4 on airway inflammation and airway remodeling in a rat asthma model

Abstract

To explore the roles of stromal cell-derived factor 1 (SDF-1) and C-X-C chemokine receptor 4 (CXCR4) on airway inflammation and airway remodeling in rat asthma models. Eighteen female SD rats were randomly divided into 3 groups (n = 6): control group, asthmatic 4 weeks group and asthmatic 8 weeks group. The rats were sensitized and inhaled ovalbumin (OVA). After the asthma model was successfully established, the airway pressure was measured. The methods of HE staining and Image-Pro Plus image analysis software were used to detect the changes of eosinophils (EOS), the perimeter of inner bronchial lumen, the wall area, the area of bronchial smooth muscle and the number of smooth muscle cells of airway walls. RT-PCR and Western-blot were used to detect the expression of SDF-1 and CXCR4 in lung tissues among the 3 groups.Immunohistochemistry was used to detect the expression of SDF-1 in airway walls. Compared with the control group, the airway responsiveness, the count of EOS, the area of bronchial wall, the area of bronchial smooth muscle, the number of smooth muscle cells of airway walls in the asthmatic 4 weeks and asthmatic 8 weeks were significantly increased, and significant difference between the 2 asthmatic groups was also observed in the above indexes (P < 0.01) .RT-PCR showed that compared with the control group (SDF-1 was 0.146 ± 0.003 and CXCR4 was 0.281 ± 0.002) , the expression of SDF-1 (0.583 ± 0.004 and 0.724 ± 0.008) and CXCR4 (0.467 ± 0.003 and 0.655 ± 0.002) in lung tissues in the asthmatic 4 weeks and asthmatic 8 weeks were significantly increased (P < 0.01) . In addition, compared with the asthmatic 4 weeks group, the expression of SDF-1 and CXCR4 in lung tissues in the 8 weeks asthmatic group were significantly increased (P < 0.01) . Compared with the control group (0.180 ± 0.009) , the expression of SDF-1 in airway walls in the asthmatic 4 weeks and asthmatic 8 weeks groups (0.270 ± 0.006 and 0.350 ± 0.009) were significantly increased (P < 0.01) . In addition, compared with the asthmatic 4 weeks group, the expression of SDF-1 in airway walls in the 8 weeks asthmatic group was significantly increased (P < 0.01) . The expression of SDF-1 and CXCR4 was correlated positively with the airway responsiveness, the number of EOS, the area of bronchial wall, the area of bronchial smooth muscle and the number of smooth muscle cells of airway walls (P < 0.01). SDF-1/CXCR4 axis may play a key role in airway inflammation and airway remodeling of asthma.