Abstract
Activated macrophages play an important role in many inflammatory diseases including septic shock and atherosclerosis. However, the molecular mechanisms limiting macrophage activation are not completely understood. Members of the tripartite motif (TRIM) family have recently emerged as important players in innate immunity and antivirus. Here, we systematically analyzed mRNA expressions of representative TRIM molecules in human THP1-derived macrophages activated by different toll-like receptor (TLR) ligands. Twenty-nine TRIM members were highly induced (>3 fold) by one or more TLR ligands, among which 19 of them belong to TRIM C-IV subgroup. Besides TRIM21, TRIM22 and TRIM38 were shown to be upregulated by TLR3 and TLR4 ligands as previous reported, we identified a novel group of TRIM genes (TRIM14, 15, 31, 34, 43, 48, 49, 51 and 61) that were significantly up-regulated by TLR3 and TLR4 ligands. In contrast, the expression of TRIM59 was down-regulated by TLR3 and TLR4 ligands in both human and mouse macrophages. The alternations of the TRIM proteins were confirmed by Western blot. Finally, overexpression of TRIM59 significantly suppressed LPS-induced macrophage activation, whereas siRNA-mediated knockdown of TRIM59 enhanced LPS-induced macrophage activation. Taken together, the study provided an insight into the TLR ligands-induced expressions of TRIM family in macrophages.
Highlights
Macrophages are the major components of innate immunity that enable the body to combat bacteria and other pathogens
The primer set for 72 human tripartite motif (TRIM) gene members was tested by melting curve and product sequencing before the experiments
A group of TRIM genes which belong to C-IV subgroup of TRIM family including TRIM5, 6, 14, 20, 21, 25, 34, 38, 69 or C-V subgroup including TRIM19 and TRIM56 were markedly elevated by TLR3 and TLR4 ligands, whereas TRIM59 was down-regulated by TLR3 and TLR4 ligands in THP1-derived macrophages
Summary
Macrophages are the major components of innate immunity that enable the body to combat bacteria and other pathogens. Several systematic analyses suggest that many TRIM proteins are implicated in the regulation of innate immune pathways and anti-viral activities[8,9,10,11]. Rajsbaum et al found that the genes encoding a subset of TRIM proteins located on chromosome 7 were up-regulated by type I IFN in macrophages/ DC, suggesting that they may have anti-viral functions[11]. TRIM30 induces the lysosomal degradation of TAB2 and TAB3, thereby negatively regulating NF-κB induction in the LPS-triggered TLR4 signaling pathway[19]. TRIM21 negatively regulates TLR3, −4, −7, and −9 and RLR signaling pathways by modulating the activities of IKKs and interferon regulatory factors (IRFs)[20,21]. We systematically profiled the expressions of TRIM gene family in human THP1-derived macrophages activated by different TLR ligands. The function of TRIM59 in macrophage activation was further studied
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.