tetano
Editor, Senior Moderator
Virulence
. 2022 Dec;13(1):502-513.
doi: 10.1080/21505594.2022.2040188.
AP-1 signaling pathway promotes pro-IL-1β transcription to facilitate NLRP3 inflammasome activation upon influenza A virus infection
Pin Wan[SUP] 1 [/SUP], Simeng Zhang[SUP] 2 [/SUP], Zhihui Ruan[SUP] 1 [/SUP], Xueli Liu[SUP] 3 [/SUP], Ge Yang[SUP] 1 [/SUP], Yaling Jia[SUP] 2 [/SUP], Yongkui Li[SUP] 1 2 [/SUP], Pan Pan[SUP] 4 [/SUP], Wenbiao Wang[SUP] 2 [/SUP], Geng Li[SUP] 1 2 [/SUP], Xulin Chen[SUP] 1 2 [/SUP], Zhixin Liu[SUP] 5 [/SUP], Qiwei Zhang[SUP] 1 2 [/SUP], Zhen Luo[SUP] 1 2 [/SUP], Jianguo Wu[SUP] 1 2 3 4 [/SUP]
Affiliations
Abstract
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.
Keywords: AP-1 signaling pathway; NLRP3 inflammasome; influenza A virus, IAV; interleukin-1β, IL-1β; type I interferon.
. 2022 Dec;13(1):502-513.
doi: 10.1080/21505594.2022.2040188.
AP-1 signaling pathway promotes pro-IL-1β transcription to facilitate NLRP3 inflammasome activation upon influenza A virus infection
Pin Wan[SUP] 1 [/SUP], Simeng Zhang[SUP] 2 [/SUP], Zhihui Ruan[SUP] 1 [/SUP], Xueli Liu[SUP] 3 [/SUP], Ge Yang[SUP] 1 [/SUP], Yaling Jia[SUP] 2 [/SUP], Yongkui Li[SUP] 1 2 [/SUP], Pan Pan[SUP] 4 [/SUP], Wenbiao Wang[SUP] 2 [/SUP], Geng Li[SUP] 1 2 [/SUP], Xulin Chen[SUP] 1 2 [/SUP], Zhixin Liu[SUP] 5 [/SUP], Qiwei Zhang[SUP] 1 2 [/SUP], Zhen Luo[SUP] 1 2 [/SUP], Jianguo Wu[SUP] 1 2 3 4 [/SUP]
Affiliations
- PMID: 35300578
- DOI: 10.1080/21505594.2022.2040188
Abstract
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.
Keywords: AP-1 signaling pathway; NLRP3 inflammasome; influenza A virus, IAV; interleukin-1β, IL-1β; type I interferon.