A Novel Accessory Molecule Trim59 Involved in Cytotoxicity of BCG-Activated Macrophages

Zhao, Xiaohong; Liu, Qihui; Du, Baiqiu; Li, Peng; Cui, Qu; Han, Xiao; Du, Binghai; Yan, Dongmei; Zhu, X. D.

doi:10.1007/s10059-012-0089-z

Cited by 18 publications

(7 citation statements)

References 30 publications

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“…TRIM59 can also regulate autophagy by modulating both the transcription and ubiquitination of BECN1 [42]. Interestingly, we found that TRIM59 expression is induced in BCG-stimulated macrophages and mediates a cytotoxic effect by direct cell contact on MCA207 fibrosarcoma cells [20]. In the present work, TRIM59 deficiency stimulated the metastatic potential of melanoma cells, suggesting that expression of TRIM59 in macrophages may have antitumor effects.…”

Section: Discussionmentioning

confidence: 49%

“…Our previous work showed that TRIM59 may be an essential molecule underlying the cytotoxic effect of bacillus Calmette Guérin (BCG) -activated macrophages on MCA207 fibrosarcoma cells [20]. In preliminary experiments, we also observed that the supernatant of RAW264.7 cells overexpressing TRIM59 had a strong cytotoxic effect on mouse B16 melanoma cell lines, and this effect was attenuated by a TRIM59-blockingantibody (data not shown).…”

Section: Introductionmentioning

confidence: 89%

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TRIM59 loss in M2 macrophages promotes melanoma migration and invasion by upregulating MMP-9 and Madcam1

Tian

Guo

Zhu

et al. 2019

Aging

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The culture supernatant from macrophages overexpressing TRIM59 has a cytotoxic effect on melanoma, but the mechanism remains unclear. To investigate whether deletion of TRIM59 in macrophages affects the metastatic potential of melanoma cells, we polarized control and TRIM59-deficient bone marrow-derived macrophages to the M2 phenotype and collected the respective conditioned media (CM). Exposure to CM from TRIM59-/--M2 cultures significantly promoted migration and invasion by B16-F0 and B16-F10 cells. Cytokine profiling indicated a ~15-fold increase in TNF-α production in CM from TRIM59-/--M2 cultures, and neutralizing TNF-α activity abrogated the referred stimulatory effects on cell motility. Transcriptome analysis revealed significant upregulation of MMP-9 and Madcam1 in melanoma cells exposed to TRIM59-/--M2 CM. Inhibitory experiments determined that these changes were also TNF-α-dependent and mediated by activation of ERK signaling. Independent knockdown of MMP9 and Madcam1 in B16-F10 cells impeded epithelial-mesenchymal transition and inhibited subcutaneous tumor growth and formation of metastatic lung nodules in vivo. These data suggest TRIM59 expression attenuates the tumor-promoting effect of tumor-associated macrophages, most of which resemble the M2 phenotype. Moreover, they highlight the relevance of TRIM59 in macrophages as a potential regulator of tumor metastasis and suggest TRIM59 could serve as a novel target for cancer immunotherapy.

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Section: Discussionmentioning

confidence: 49%

Section: Introductionmentioning

confidence: 89%

TRIM59 loss in M2 macrophages promotes melanoma migration and invasion by upregulating MMP-9 and Madcam1

Tian

Guo

Zhu

et al. 2019

Aging

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“…Trim59, a member of the tripartite motif (TRIM)-containing protein superfamily, is characterized by one or two zinc binding motifs, an associated coiled-coil region and a RING-finger domain 10 . Previous studies show that Trim59 participates in many pathological regulation such as inflammation 11 , cytotoxicity 12 , and especially tumorigenesis 13 . Here we found that Trim59 plays a vital role in mouse early embryonic development stage.…”

Section: Introductionmentioning

confidence: 99%

Embryonic lethality in mice lacking Trim59 due to impaired gastrulation development

et al. 2018

Cell Death Dis

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TRIM family members have been implicated in a variety of biological processes such as differentiation and development. We here found that Trim59 plays a critical role in early embryo development from blastocyst stage to gastrula. There existed delayed development and empty yolk sacs from embryonic day (E) 8.5 in Trim59−/− embryos. No viable Trim59−/− embryos were observed beyond E9.5. Trim59 deficiency affected primary germ layer formation at the beginning of gastrulation. At E6.5 and E7.5, the expression of primary germ layer formation-associated genes including Brachyury, lefty2, Cer1, Otx2, Wnt3, and BMP4 was reduced in Trim59−/− embryos. Homozygous mutant embryonic epiblasts were contracted and the mesoderm was absent. Trim59 could interact with actin- and myosin-associated proteins. Its deficiency disturbed F-actin polymerization during inner cell mass differentiation. Trim59-mediated polymerization of F-actin was via WASH K63-linked ubiquitination. Thus, Trim59 may be a critical regulator for early embryo development from blastocyst stage to gastrula through modulating F-actin assembly.

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“…In conclusion, we proved that TRIM59 in myeloid derived macrophages protected mice from sepsis by regulating inflammation and phagocytosis. Our previous study found that TRIM59 promoted phagocytosis activity in the RAW264.7 cell line (21). Phagocytosis plays an important role in bacteria invasion, so we hypothesized that TRIM59 could affect sepsis by regulating macrophage phagocytosis.…”

Section: Discussionmentioning

confidence: 94%

TRIM59 Protects Mice From Sepsis by Regulating Inflammation and Phagocytosis in Macrophages

et al. 2020

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Sepsis is associated with bacterial invasion and inflammation and has a high mortality rate. Previous studies have demonstrated that tripartite motif 59 (TRIM59) was involved in NF-κB signaling and could promote phagocytosis of macrophages, but the role of TRIM59 in sepsis is still unknown. In our study, we found that TRIM59 was downregulated in lipopolysaccharide (LPS)-stimulated bone marrow-derived macrophages (BMDMs). In the cecal ligation and puncture (CLP) sepsis mice model, the mortality of Trim59 flox/flox Lyz-Cre (Trim59-cKO) mice was higher, the immune cell infiltration and damage of liver and lung were more severe, and bacteria burden was increased. We also found that TRIM59 altered the production of pro-inflammation cytokines, as well as macrophage phagocytosis ability. Further analysis indicated that NF-κB signal pathway and Fcγ receptors might be involved in these regulations. Our study demonstrated for the first time that TRIM59 protects mice from sepsis by regulating inflammation and phagocytosis in macrophages.

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A Novel Accessory Molecule Trim59 Involved in Cytotoxicity of BCG-Activated Macrophages

Cited by 18 publications

References 30 publications

TRIM59 loss in M2 macrophages promotes melanoma migration and invasion by upregulating MMP-9 and Madcam1

TRIM59 loss in M2 macrophages promotes melanoma migration and invasion by upregulating MMP-9 and Madcam1

Embryonic lethality in mice lacking Trim59 due to impaired gastrulation development

TRIM59 Protects Mice From Sepsis by Regulating Inflammation and Phagocytosis in Macrophages

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