Wuhu Decoction Regulates Dendritic Cell Autophagy in the Treatment of Respiratory Syncytial Virus (RSV)-Induced Mouse Asthma by AMPK/ULK1 Signaling Pathway
Xingyu Chen, Yinhe Luo, Mengqing Wang, Le Sun, Kailing Huang, Yan Li, Yingying Chen, Yi Ding, Xin Zhang, Luojia Jiao, Jingyi Yang, Ting Huang
(Hunan University of Chinese Medicine, Changsha, Hunan, China (mainland))
Med Sci Monit 2019; 25:5389-5400
Dendritic cell autophagy plays a pivotal role in asthma. Wuhu decoction can significantly improve respiratory syncytial virus (RSV) bronchiolitis and delay its development into asthma. The aim of the present study was to explore the therapeutic effect and mechanism of Wuhu decoction on RSV -induced asthma in mice.
MATERIAL AND METHODS: Establishment of asthmatic mice model was induced by RSV. Hematoxylin-eosin staining, periodic acid-Schiff (PAS) staining, and Masson trichrome staining were performed to observe pathological changes in the lungs. The levels of CD4⁺ T, CD8⁺ T, and CD4⁺ CD25⁺ T in blood were analyzed by flow cytometry. The contents of interleukin (IL)-4, interferon-gamma (IFN-γ), IL-10, and IL-13 in serum were measured by enzyme-linked immunosorbent assay (ELISA). The number of autophagosomes in dendritic cells (DCs) of lung tissue was observed by transmission electron microscope. The DCs of lung tissue were isolated by magnetic bead sorting. The levels of LC3-II, Beclin-1, and LC3-I in DCs and MMP-9, TIMP-1, AMPK, p-AMPK, ULK1, and LK1 expression in lung tissues were detected by western blot. Real-time polymerase chain reaction (PCR) detected the expression of AMPK and ULK1 genes.
RESULTS: Wuhu decoction can effectively alleviate chronic airway inflammation and airway remodeling and reduce airway hyperresponsiveness. Moreover, Wuhu decoction can significantly enhance the level of autophagy in DCs of lung tissue and promote the expression of AMPK and ULK1 in lung tissue.
CONCLUSIONS: Wuhu decoction may improve the RSV-induced asthmatic symptoms by enhancing autophagy of DCs in lung tissue dependent on the AMPK/ULK1 signaling pathway.
Keywords: Asthma, Autophagy, Dendritic Cells, Respiratory Syncytial Viruses