AP-1 signaling pathway promotes pro-IL-1β transcription to facilitate NLRP3 inflammasome activation upon influenza A virus infection

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
• influenza A virus, IAV
• interleukin-1β, IL-1β
• NLRP3 inflammasome
• type I interferon

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article and/or its supplementary materials.

Notes

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2. The spelling of ”in” is wrong. ”in” is replaced with ”In”.

Additional information

Funding

This work was sponsored by the National Natural Science Foundation of China [81730061 to JW and 32070148 to ZL], Guangdong Province Pearl River Talent Plan Innovation and Entrepreneurship Team Project [2017ZT07Y580 to JW], Guangdong Basic and Applied Basic Research Foundation [2019A1515011073 to ZL], and Guangzhou Basic Research Program - Basic and Applied Basic Research Project [202102020260 to ZL].