E3 ubiquitin ligase tripartite motif 7 positively regulates the TLR4-mediated immune response via its E3 ligase domain in macrophages. (May 2019)

• Record Type: Journal Article
• Authors: Lu, Mingfeng; Zhu, Xuhui; Yang, Zhizhou; Zhang, Wei; Sun, Zhaorui; Ji, Qijian; Chen, Xin; Zhu, Jin; Wang, Changjun; Nie, Shinan
• Is Part Of: Molecular immunology. Volume 109(2019:May)
• Page Start: 126
• Page End: 133
• Publication Date: 2019-05
• Subjects: TRIM7 -- TLR4 -- LPS -- E3 ligase activity -- RING domain; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2019.01.015
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: TRIM7 is highly expressed in antigen-presenting cells. TRIM7 preferentially promotes LPS-induced production of proinflammatory cytokines and type I IFN in macrophages. TRIM7 enhances TLR4 signaling in macrophages. TRIM7 promotes TLR4 activation through its E3 ligase activity. Abstract: Members of the tripartite motif (TRIM) family as E3 ubiquitin ligases have been regarded as critical regulators of innate immunity and antiviral response. However, the role of TRIM7 is still elusive. Here, we provide evidence for the importance of TRIM7 in regulation of the TLR4-mediated innate response. In detail, we find that TRIM7 is highly expressed in antigen-presenting cells like macrophages. Knockdown of TRIM7 clearly inhibits the LPS-induced production of IFN-β, TNF-α and IL-6 in macrophages. Conversely, forced expression of TRIM7 could exert an opposite effect on these pro-inflammatory cytokines. Further analysis indicates that such effect is mediated by the TLR4-associated signaling pathways including MAPKs, NF-κB and IRF3-involved pathways. Truncation of the E3 ligase domain on TRIM7 may reduce the production of pro-inflammatory cytokines, suggesting a critical role of this domain in the regulation of LPS-initiated innate response. Taken together, we report here that TRIM7 may facilitate the TLR4-mediated innate response via its E3 ligase domain in macrophages, which provides new insight into the mechanistic role of TRIM7 in innate immunity.