Kukoamine A Improves Mycoplasma pneumoniae Pneumonia by Regulating miR-222-3p/Superoxide Dismutase 2

Abstract

Mycoplasma pneumoniae pneumonia (MPP) represents a common respiratory disease in children patients. Kukoamine A (KuA) is a spermine alkaloid found in the Chinese herb Cortex Lycii radices, which has a variety of pharmacological properties. However, no study has been reported on the role of KuA in MPP. Exosomes, a type of lipid bilayer-enclosed extracellular vesicles, can be delivered to the target cells, where they regulate function and physiology. With the use of human alveolar basal epithelial cells (HABECs) as an in vitro model, in this study, we sought to characterize the changes in levels of superoxide dismutase 2 (SOD2) and proinflammatory cytokines including IL-6 and TNF-α in HABECs in response to exosomes, which were isolated from peripheral blood serum of MPP patients. We found that, compared to normal, MPP patients exhibited a significant up-regulated miR-222-3p. Further, exosomal miR-222-3p downregulated SOD2 activity but promoted nuclear NF-κB activity and expression of IL-6 and TNF-α in HABECs, ultimately leading to an oxidative stress condition. Interestingly, such stimulating effects were attenuated by the pretreatment of KuA. This study suggests a critical role possessed by KuA in MPP by regulating the miR-222-3p/SOD2 axis, which represents a promising strategy for the treatment of MPP.