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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\u03b2, TNF-\u03b1, IL-6, CCL2, and CCL5, both in vitro and in vivo. Autophagy-mediated inflammatory responses involved the activation of NF-\u03baB 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-\u03baB also promoted H5N1pp-induced autophagosome formation. These data indicated a positive feedback loop between autophagy and NF-\u03baB 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. <\/jats:p>","DOI":"10.1152\/ajplung.00147.2013","type":"journal-article","created":{"date-parts":[[2013,11,16]],"date-time":"2013-11-16T05:39:02Z","timestamp":1384580342000},"page":"L183-L195","source":"Crossref","is-referenced-by-count":76,"title":["Autophagy mediates avian influenza H5N1 pseudotyped particle-induced lung inflammation through NF-\u03baB and p38 MAPK signaling pathways"],"prefix":"10.1152","volume":"306","author":[{"given":"Hong","family":"Pan","sequence":"first","affiliation":[{"name":"Key Laboratory of Health Informatics of Chinese Academy of Sciences, Guangdong Key Laboratory of Nanomedicine, Shenzhen Innovative Pharmacology and Biotherapy Pre-clinical Test Public Service Platform, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, 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