M1 and M2 macrophages derived from THP-1 cells differentially modulate the response of cancer cells to etoposide

Genin, Marie; François, Clément; Fattaccioli, Antoine; Raes, Martine; Michiels, Carine

doi:10.1186/s12885-015-1546-9

Cited by 792 publications

(686 citation statements)

References 41 publications

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“…This result was in accordance with several in vitro studies, indicating THP-1-derived macrophages as a well-characterized model for studying macrophage polarization [16,17,23–25]. …”

Section: Resultssupporting

confidence: 92%

Alternatively Activated (M2) Macrophage Phenotype Is Inducible by Endothelin-1 in Cultured Human Macrophages

et al. 2016

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BackgroundAlternatively activated (M2) macrophages are phenotypically characterized by the expression of specific markers, mainly macrophage scavenger receptors (CD204 and CD163) and mannose receptor-1 (CD206), and participate in the fibrotic process by over-producing pro-fibrotic molecules, such as transforming growth factor-beta1 (TGFbeta1) and metalloproteinase (MMP)-9. Endothelin-1 (ET-1) is implicated in the fibrotic process, exerting its pro-fibrotic effects through the interaction with its receptors (ETA and ETB). The study investigated the possible role of ET-1 in inducing the transition from cultured human macrophages into M2 cells.MethodsCultured human monocytes (THP-1 cell line) were activated into macrophages (M0 macrophages) with phorbol myristate acetate and subsequently maintained in growth medium (M0-controls) or treated with either ET-1 (100nM) or interleukin-4 (IL-4, 10ng/mL, M2 inducer) for 72 hours. Similarly, primary cultures of human peripheral blood monocyte (PBM)-derived macrophages obtained from healthy subjects, were maintained in growth medium (untreated cells) or treated with ET-1 or IL-4 for 6 days. Both M0 and PBM-derived macrophages were pre-treated with ET receptor antagonist (ETA/BRA, bosentan 10-5M) for 1 hour before ET-1 stimulation. Protein and gene expression of CD204, CD206, CD163, TGFbeta1 were analysed by immunocytochemistry, Western blotting and quantitative real time polymerase chain reaction (qRT-PCR). Gene expression of interleukin(IL)-10 and macrophage derived chemokine (CCL-22) was evaluated by qRT-PCR. MMP-9 production was investigated by gel zymography.ResultsET-1 significantly increased the expression of M2 phenotype markers CD204, CD206, CD163, IL-10 and CCL-22, and the production of MMP-9 in both cultures of M0 and PBM-derived macrophages compared to M0-controls and untreated cells. In cultured PBM-derived macrophages, ET-1 increased TGFbeta1 protein and gene expression compared to untreated cells. The ET-1-mediated effects were contrasted by ETA/BRA treatment in both cultured cell types.ConclusionET-1 seems to induce the M2 phenotype in cultured human macrophages, a process apparently contrasted by the action of the ETA/BRA, suggesting possible clinical implications in those fibrotic diseases characterized by increased ET-1 concentrations, such as systemic sclerosis but also type 2 diabetes.

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“…This result was in accordance with several in vitro studies, indicating THP-1-derived macrophages as a well-characterized model for studying macrophage polarization [16,17,23–25]. …”

Section: Resultssupporting

confidence: 92%

Alternatively Activated (M2) Macrophage Phenotype Is Inducible by Endothelin-1 in Cultured Human Macrophages

et al. 2016

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“…In accordance with previously published data (31), this showed that CCL18 was selectively induced in M2 cells (Supplemental Figure 1A). In M0 ( Figure 3A) and M2 (Supplemental Figure 2B) cells, 0.5 g/mL (but not 0.05 g/mL), recombinant CCL18 induced an increase in previously reported response genes including CCL2 and CCL3, an effect that was not observed in M1 cells (Supplemental Figure 2A).…”

Section: Functional Studies Of Ccl18 In Human Macrophages and Adipocytessupporting

confidence: 93%

Adipose and Circulating CCL18 Levels Associate With Metabolic Risk Factors in Women

Hogling

Petrus

Gao

et al. 2016

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context: Cardiometabolic complications in obesity may be linked to white adipose tissue (WAT) dysfunction. Transcriptomic studies of Sc WAT have reported that CCL18, encoding the CC chemokine ligand 18 (CCL18), is increased in obesity/insulin resistance but its functional role is unknown.Objective: Our objectives were to determine if CCL18 is secreted from Sc WAT and if secreted and/or serum levels associate with metabolic phenotypes. We also planned to define the primary cellular source and if CCL18 exerts effects on adipocytes.Design: This is a cohort study. Setting:The study took place in an outpatient academic clinic.Participants: A total of 130 obese women scheduled for bariatric surgery and 35 nonobese controls were included.Methods: Insulin sensitivity was assessed by hyperinsulinemic euglycemic clamp or homeostasis model assessment. CCL18 was analyzed in serum/WAT incubates by ELISA. Effects of recombinant CCL18 was determined in cultures of primary human adipocytes and the monocyte cell line THP-1 differentiated into M0/M1/M2 macrophages. Main Outcome Measure: Association with metabolic risk factors was measured.Results: CCL18 was secreted from WAT and the levels correlated positively with insulin resistance, Adult Treatment Panel III risk score and plasma triglycerides, independent of body mass index and better than other established adipocytokines. In 80 obese women, S-CCL18 levels were significantly higher in insulin resistant compared with insulin sensitive subjects. In WAT CCL18 mRNA was expressed in macrophages and correlated positively with immune-related genes, particularly those enriched in M2 macrophages. While CCL18 increased cyto-/chemokine expression in M0/M2-THP-1 cells, human adipocytes showed no responses in vitro. Conclusions:Circulating and WAT-secreted CCL18 correlates with insulin resistance and metabolic risk score. Because CCL18 is macrophage-specific and associates with adipose immune gene expression, it may constitute a marker of WAT inflammation. (J Clin Endocrinol Metab 101: 4021-4029, 2016)

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“…18 THP-1 macrophages transduced with versikine-plasmid or empty-vector control were cocultured with human myeloma MM1.S cells for 48 hours and RNA-seq analysis was performed on each cell type. Remarkably, only 23 genes were differentially expressed in MM1.S cells exposed to versikine-secreting macrophages and all were upregulated: among these, 13 genes defined a type I interferon (IFN) signature ( Figure 1H).…”

Section: Resultsmentioning

confidence: 99%

Immunoregulatory roles of versican proteolysis in the myeloma microenvironment

Hope

Foulcer

Jagodinsky

et al. 2016

Blood

126

107

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• Interplay between myeloma niche stromal cells and myeloid cells generates versikine, a novel damageassociated molecular pattern.• Versikine may promote antigen-presenting cell maturation and CD8 1 T-cell activation/recruitment to the tumor bed.Myeloma immunosurveillance remains incompletely understood. We have demonstrated proteolytic processing of the matrix proteoglycan, versican (VCAN), in myeloma tumors. Whereas intact VCAN exerts tolerogenic activities through Toll-like receptor 2 (TLR2) binding, the immunoregulatory consequences of VCAN proteolysis remain unknown. Here we show that human myeloma tumors displaying CD81 infiltration/aggregates underwent VCAN proteolysis at a site predicted to generate a glycosaminoglycan-bereft N-terminal fragment, versikine. Myeloma-associated macrophages (MAMs), rather than tumor cells, chiefly produced V1-VCAN, the precursor to versikine, whereas stromal cell-derived ADAMTS1 was the most robustly expressed VCAN-degrading protease. Purified versikine induced early expression of inflammatory cytokines interleukin 1b (IL-1b) and IL-6 by human myeloma marrow-derived MAMs. We show that versikine signals through pathways both dependent and independent of Tpl2 kinase, a key regulator of nuclear factor kB1-mediated MAPK activation in macrophages. Unlike intact VCAN, versikine-induced Il-6 production was partially independent of Tlr2. In a model of macrophage-myeloma cell crosstalk, versikine induced components of "T-cell inflammation," including IRF8-dependent type I interferon transcriptional signatures and T-cell chemoattractant CCL2. Thus the interplay between stromal cells and myeloid cells in the myeloma microenvironment generates versikine, a novel bioactive damage-associated molecular pattern that may facilitate immune sensing of myeloma tumors and modulate the tolerogenic consequences of intact VCAN accumulation. Therapeutic versikine administration may potentiate T-cell-activating immunotherapies. (Blood. 2016;128(5):680-685)

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M1 and M2 macrophages derived from THP-1 cells differentially modulate the response of cancer cells to etoposide

Cited by 792 publications

References 41 publications

Alternatively Activated (M2) Macrophage Phenotype Is Inducible by Endothelin-1 in Cultured Human Macrophages

Alternatively Activated (M2) Macrophage Phenotype Is Inducible by Endothelin-1 in Cultured Human Macrophages

Adipose and Circulating CCL18 Levels Associate With Metabolic Risk Factors in Women

Immunoregulatory roles of versican proteolysis in the myeloma microenvironment

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