期刊
MOLECULAR IMMUNOLOGY
卷 130, 期 -, 页码 69-76出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2020.12.022
关键词
RIG-I; Cytokines; NF-kappa B; Inflammatory response; Macrophages
资金
- National Natural Science Foundation of China [31670914, U1801283, 31870908]
- Shenzhen Science and Technology Innovation Commission [JCYJ20180507182253653]
- Zhejiang Provincial Natural Science Foundation of China [LZ17H100001]
- Guangdong Provincial Science and Technology Program [2019B030301009]
USP14 acts as a negative regulator of RIG-I-mediated inflammatory response by inhibiting NF-kappa B activation and deubiquitinating K63-linked RIG-I, leading to decreased pro-inflammatory cytokine production in macrophages and HeLa cells. Additionally, USP14 inhibitor IU1 significantly promotes pro-inflammatory cytokines production in VSV-infected mice in vivo.
Ubiquitin specific protease 14 (USP14) is a regulator of protein deubiquitination and proteasome activation, and has been implicated in negative regulation of type I IFN signaling pathway. However, the effect of USP14 on RNA virus-related inflammatory response has not been studied. Retinoic acid-inducible gene I (RIG-I) is the important pattern recognition receptor of the innate immunity to detect RNA viruses or intracellular Poly(I:C)-LMW. Here, we reported that USP14 knockdown increased pro-inflammatory cytokines production in macrophages upon VSV infection or intracellular Poly(I:C)-LMW stimulation. USP14-overexpressed HeLa cells exhibited a decrease in RIG-I-mediated IL-6 and TNF-alpha expression. IU1, USP14 inhibitor, significantly promotes pro-inflammatory cytokines production in VSV-infected mice in vivo. Furthermore, USP14 was also found to inhibit the RIG-Itriggered NF-kappa B activation by deubiquitinating K63-linked RIG-I. Thus, our results demonstrate that USP14 is a negative regulator of RIG-I-mediated inflammatory response.
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