Autophagy mediates avian influenza H5N1 pseudotyped particle-induced lung inflammation through NF-κB and p38 MAPK signaling pathways

	Autophagy mediates avian influenza H5N1 pseudotyped particle-induced lung inflammation through NF-κB and p38 MAPK signaling pathways
	Pan, Hong; Zhang, Yijuan; Luo, Zichao; Li, Ping; Liu, Lanlan; Wang, Ce; Wang, Hanzhong; Li, Hongchang; Ma, Yifan
刊名	AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
	2014
英文摘要	Since avian influenza virus H5N1-induced hypercytokemia plays a key role in acute lung injury, understanding its molecular mechanism is highly desirable for discovering therapeutic targets against H5N1 infection. In the present study, we investigated the role of autophagy in H5N1-induced lung inflammation by using H5N1 pseudotyped viral particles (H5N1pps). The results showed that H5N1pps significantly induced autophagy both in A549 human lung epithelial cells and in mouse lung tissues, which was primarily due to hemagglutinin (HA) of H5N1 virus. Blocking autophagy with 3-methyladenine (an autophagy inhibitor) or siRNA knockdown of autophagy-related genes (beclin1 and atg5) dramatically attenuated H5N1pp-induced proinflammatory cytokines and chemokines, such as IL-1 beta, TNF-alpha, IL-6, CCL2, and CCL5, both in vitro and in vivo. Autophagy-mediated inflammatory responses involved the activation of NF-kappa B and p38 MAPK signaling pathways, which required the presence of clathrin but did not rely on p62 or autophagosome-lysosome fusion. On the other hand, the activation of NF-kappa B also promoted H5N1pp-induced autophagosome formation. These data indicated a positive feedback loop between autophagy and NF-kappa B signaling cascade, which could exacerbate H5N1pp-induced lung inflammation. Our data demonstrated an essential role of autophagy in H5N1pp-triggered inflammatory responses, and targeting the autophagic pathway could be a promising strategy to treat H5N1 virus-caused lung inflammation.
收录类别	SCI
原文出处	http://ajplung.physiology.org/content/306/2/L183
语种	英语
内容类型	期刊论文
源URL	[http://ir.siat.ac.cn:8080/handle/172644/6090]
专题	深圳先进技术研究院_医药所
作者单位	AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
推荐引用方式 GB/T 7714	Pan, Hong,Zhang, Yijuan,Luo, Zichao,et al. Autophagy mediates avian influenza H5N1 pseudotyped particle-induced lung inflammation through NF-κB and p38 MAPK signaling pathways[J]. AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY,2014.
APA	Pan, Hong.,Zhang, Yijuan.,Luo, Zichao.,Li, Ping.,Liu, Lanlan.,...&Ma, Yifan.(2014).Autophagy mediates avian influenza H5N1 pseudotyped particle-induced lung inflammation through NF-κB and p38 MAPK signaling pathways.AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY.
MLA	Pan, Hong,et al."Autophagy mediates avian influenza H5N1 pseudotyped particle-induced lung inflammation through NF-κB and p38 MAPK signaling pathways".AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY (2014).