AP-1 signaling pathway promotes pro-IL-1β transcription to facilitate NLRP3 inflammasome activation upon influenza A virus infection
Pin Wan,
Simeng Zhang,
Zhihui Ruan,
Xueli Liu,
Ge Yang,
Yaling Jia,
Yongkui Li,
Pan Pan,
Wenbiao Wang,
Geng Li,
Xulin Chen,
Zhixin Liu,
Qiwei Zhang,
Zhen Luo,
Jianguo Wu
Affiliations
Pin Wan
Foshan Institute of Medical Microbiology, Foshan, China
Simeng Zhang
Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China
Zhihui Ruan
Foshan Institute of Medical Microbiology, Foshan, China
Xueli Liu
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China
Ge Yang
Foshan Institute of Medical Microbiology, Foshan, China
Yaling Jia
Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China
Yongkui Li
Foshan Institute of Medical Microbiology, Foshan, China
Pan Pan
The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
Wenbiao Wang
Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China
Geng Li
Foshan Institute of Medical Microbiology, Foshan, China
Xulin Chen
Foshan Institute of Medical Microbiology, Foshan, China
Zhixin Liu
Department of Infectious Diseases, Department of Respiratory, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China
Qiwei Zhang
Foshan Institute of Medical Microbiology, Foshan, China
Zhen Luo
Foshan Institute of Medical Microbiology, Foshan, China
Jianguo Wu
Foshan Institute of Medical Microbiology, Foshan, China
NLRP3 inflammasome mainly controls interleukin-1β (IL-1β) secretion, leading to cell death called pyroptosis constituting a major antiviral host defense and inflammatory diseases upon viral infection. The RAF-MEK1/2-ERK1/2 cascade and downstream c-Jun/Fos and Activator protein-1 (AP1) signaling pathway control the degree of inflammatory response. Influenza A virus (IAV) infection is known to stimulate NLRP3 inflammasome activation and inflammatory responses. Nevertheless, the detailed mechanism by which IAV induces NLRP3 inflammasome activation involved in transcription of pro-IL-1β mRNA remains elusive. In our study, we found that IAV infection promotes pro-IL-1β mRNA transcription and activates NLRP3 inflammasome. Detailed studies reveal that type I interferon (IFN-α/IFN-β) as well as U0126 (a selective inhibitor of MEK-1 and MEK-2) typically inhibit IAV-mediated NLRP3 inflammasome activation via downregulating pro-IL-1β mRNA. Moreover, knock-down of c-Jun decreases pro-IL-1β mRNA and inhibits NLRP3 inflammasome activation upon IAV infection. Overall, the findings uncover that AP-1 signaling pathway promotes NLRP3 inflammasome activation upon IAV infection, which provides a new idea for the therapy of NLRP3 inflammasome-associated inflammatory diseases.
