Berberine mediates NF-κB/LCN2 signaling pathway to improve Th17/Treg cell imbalance induced by COPD
Objective To establish a rat model of chronic obstructive pulmonary disease(COPD),to explore whether berberine can improve the imbalance of Th17/Treg cells induced by COPD by regulating NF-κB/LCN2 signaling pathway.Methods Fifty Wistar rats were randomly divided into Control group(control group),chronic obstructive pulmonary disease group(COPD group),Berberine group(Berberine group),berberine+overexpression control group(Berberine+ov-NC group)and berberine+overexpression LCN2 group(Berberine+ov-LCN2 group),with 10 rats in each group.Western blotting was used to detect the expression of p-NF-κB,LCN2,IL-17 and IL-10 in lung tissue.HE staining was used to observe the pathological changes of lung tissue in rats.The ratio of Th17/Treg cells in peripheral blood of rats was detected by flow cytometry.The levels of IL-17 and IL-10 in serum of rats were detected by ELISA.Results In the control group,the lung tissue structure was intact;compared with the control group,the lung tissue structure of rats in COPD group was damaged,the expressions of p-NF-κB and LCN2 protein in lung tissue were significantly increased,the proportion of Th17 cells in peripheral blood was significantly increased,the proportion of Treg cells was significantly decreased,the level of IL-17 in serum and the expression of IL-17 protein in lung tissue were significantly increased,and the level of IL-10 in serum and the expression of IL-10 protein in lung tissue were significantly decreased(P<0.05).Compared with COPD group,Berberine group and Berberine+ov-NC group improved lung tissue injury,significantly decreased the expression of p-NF-κB and LCN2 proteins in lung tissue,significantly decreased the proportion of Th17 cells in peripheral blood,significantly increased the proportion of Treg cells,significantly decreased the level of IL-17 in serum and the expression of IL-17 protein in lung tissue(P<0.05).Compared with Berberine group and Berberine+ov-NC group,Berberine+ov-LCN2 group has more lung injury,higher expression of LCN2 protein in lung tissue,higher proportion of Th17 cells in peripheral blood,lower proportion of Treg cells,higher levels of IL-17 in serum and IL-17 protein expression in lung tissue,and higher levels of IL-10 in serum and IL-10 protein in lung tissue(P<0.05).Conclusion Berberine treatment can improve lung injury and Th17/Treg cell imbalance in COPD rats by down-regulating the expression of LCN2,and its mechanism may be related to the inhibition of NF-κB/LCN2 signaling pathway.
COPDBerberineTh17/Treg cell imbalanceNF-κB/LCN2 signal pathway