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Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
Published on: May 22, 2014
RNA m6A reader YTHDF1 facilitates inflammation via enhancing NLRP3 translation
Wei-Yuan Hao1, Yan Lou2, Guo-Ying Hu3
1Department of Intervention, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, 1 East Banshan Road, Hangzhou, 310022, Zhejiang, China.
Abstract:
N6-methyladenosine (m6A) modification of mRNAs is involved in multiple essential biological processes, dynamically regulated by m6A "writers", "erasers", and "readers". Yet, the detailed functional roles of RNA m6A reader proteins, such as YTHDFs, are largely unknown. Herein we show that YTHDF1 promotes pro-inflammatory IL-1β production in macrophages during bacterial infections. YTHDF1 overexpression promotes NLRP3 translation. In vivo knockdown of YTHDF1 facilitates survival in a mouse model of sepsis. Thus, YTHDF1 participates in inflammatory responses and subsequent injuries, serving as a new potential therapeutic target in clinical treatment of inflammatory diseases.
Insights
YTHDF1, an RNA m6A reader, promotes inflammatory cytokine IL-1β production during bacterial infections. Inhibiting YTHDF1 improves survival in sepsis models, suggesting it as a therapeutic target for inflammatory diseases.
Area of Science:
- Molecular Biology
- Immunology
- Epigenetics
Background:
- N6-methyladenosine (m6A) mRNA modification is crucial for biological processes.
- m6A regulation involves "writers", "erasers", and "readers".
- Functional roles of m6A reader proteins, like YTHDFs, remain largely unclear.
Purpose of the Study:
- To elucidate the role of the RNA m6A reader protein YTHDF1 in inflammatory responses.
- To investigate YTHDF1's involvement in macrophage pro-inflammatory cytokine production.
- To assess YTHDF1 as a potential therapeutic target for inflammatory diseases.
Main Methods:
- Investigated YTHDF1 function in macrophages during bacterial infection models.
- Analyzed the effect of YTHDF1 overexpression on NLRP3 translation.
- Utilized in vivo knockdown of YTHDF1 in a mouse model of sepsis.
Main Results:
- YTHDF1 was found to promote pro-inflammatory IL-1β production in macrophages.
- Overexpression of YTHDF1 enhanced NLRP3 translation.
- In vivo knockdown of YTHDF1 significantly improved survival rates in a mouse sepsis model.
Conclusions:
- YTHDF1 plays a significant role in mediating inflammatory responses and subsequent tissue injury.
- YTHDF1 is a key mediator of IL-1β production during bacterial infections.
- YTHDF1 represents a promising therapeutic target for managing inflammatory diseases and sepsis.
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