Gene expression change induced by TIM-3/galectin-9 interaction in primary AML
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE62223 | GEO | 2014/10/10
SECONDARY ACCESSION(S): PRJNA263499
REPOSITORIES: GEO
Similar Datasets
Project description:Analysis of gene expression change after galectin-9 stimulation in primary CD34+TIM-3+ AML cells Total RNA obtained from purified CD34+TIM-3+ primary AML cells with or without recombinant human galectin-9 stimulation (20hrs) was subjected to transcriptome analysis
2014-10-10 | E-GEOD-62223 | biostudies-arrayexpress
Project description:T cell immunoglobulin and mucin-containing molecule 3 (TIM-3) exhibits unique, cell type- and context-dependent characteristics and functions. Here, we report that TIM-3 on myeloid cells plays essential roles in modulating lung inflammation. We found that myeloid cell-specific TIM-3 knock-in (FSF-TIM3/LysM-Cre+) mice have lower body weight and shorter lifespan than WT mice. Intriguingly, the lungs of FSF-TIM3/LysM-Cre+ mice display excessive inflammation and features of disease-associated pathology. We further revealed that galectin-3 levels are notably elevated in TIM-3-overexpressing lung-derived myeloid cells. Furthermore, both TIM-3 blockade and GB1107, a galectin-3 inhibitor, ameliorated lung inflammation in FSF-TIM3/LysM-Cre+/- mice. Using an LPS-induced lung inflammation model with myeloid cell-specific TIM-3 knock-out mice, we demonstrated the association of TIM-3 with both lung inflammation and galectin-3. Collectively, our findings suggest that myeloid TIM-3 is an important regulator in the lungs and that modulation of TIM-3 and galectin-3 could offer therapeutic benefits for inflammation-associated lung diseases.
2024-07-29 | GSE268660 | GEO
Project description:Purpose: To clarify the function of TIM-3 signaling in AML cells. Analysis of lentiviral shRNA-mediated knockdown of TIM-3 in TIM-3+ acute myeloid leukemia (AML) cell line, KASUMI-3. Consistent with our previous study (Kikushige et al., Cell Stem Cell 2015) revealing the presence of TIM-3/galectin-9 autocrine loop and its constitutive signaling in AML, KD of receptor,TIM-3, alone significantly impaired the proliferation of KASUMI-3 in vitro and in vivo.
2019-04-26 | GSE130328 | GEO
Project description:Investigation of whole genome gene expression level changes in a Tim-3 knockdown RAW264.7 cell, compared to control siRNA transfected RAW264.7 cell. The Tim-3 knockdown of this cell render it hyper-reactive to TLR stimulation. Tim-3 knockdown analyzed in this study are further described in Li Y, Feng J, Geng S, Geng S, Wei H, Chen G, Li X, Wang L, Wang R, Peng H, Han G, Shen B, Li Y. 2011. The N- and C-terminal carbohydrate recognition domains of galectin-9 contribute differently to its multiple functions in innate immunity and adaptive immunity. Mol Immunol. 48(4):670-7. (PID 21146220) A six chip study using total RNA recovered from Tim-3 knockdown and control RAW264.7 cells. There are 135,000 probes in a chip,each chip measures the expression level of 27526 genes of mouse from Nimblegen. Fold-change screening between the two groups obtained from the experiment. The threshold used to screen up or down regulated genes is Fold changeM-oM-<M-^-oM-<M-^]2.0
2012-12-05 | E-GEOD-42729 | biostudies-arrayexpress
Project description:Investigation of whole genome gene expression level changes in a Tim-3 knockdown RAW264.7 cell, compared to control siRNA transfected RAW264.7 cell. The Tim-3 knockdown of this cell render it hyper-reactive to TLR stimulation. Tim-3 knockdown analyzed in this study are further described in Li Y, Feng J, Geng S, Geng S, Wei H, Chen G, Li X, Wang L, Wang R, Peng H, Han G, Shen B, Li Y. 2011. The N- and C-terminal carbohydrate recognition domains of galectin-9 contribute differently to its multiple functions in innate immunity and adaptive immunity. Mol Immunol. 48(4):670-7. (PID 21146220)
2012-12-05 | GSE42729 | GEO
Project description:TIM-3 is known to be expressed on dendritic cells, monocytes, melanoma cells, mast cells and on activated Th1 cells. In activated Th1 cells, stimulating TIM-3 by one of its ligands, galectin-9, leads to apoptosis and thus it plays a central role in terminating Th1-type immune responses. Interestingly, in IgE/antigen-activated mast cells TIM-3 enhances the production of IL-13 and IL-4. To get a more complete picture about the gene expression changes induced by TIM-3 in mast cells, in vitro differentiated mouse immature mast cells were stimulated by an agonist anti-TIM-3 antibody and IgE-sensitized mouse immature mast cells were activated by antigen and an agonist anti-TIM-3 antibody for 2 or 16 hours (overnight). Experiment Overall Design: Bone marrow cells were differentiated in RPMI + 10% FCS + 5 ng/ml mouse IL-3 + 40 ng/ml mouse SCF for >4 weeks. The purity of the cell cultures was >90% at this time point (FcERIa+/c-kit+ cells). These in vitro-differentiated immature mast cells were then treated by either control goat IgG or an agonist anti-mouse TIM-3 antibody (RnD Systems, 15 ug/ml for 2 or 16 hours). For the IgE/antigen-activated mouse mast cells, these in vitro-differentiated immature mast cells were sensitized by 5 ug/ml anti-DNP IgE (Sigma) for 1 hour and then treated with 100 ng/ml DNP-HSA (antigen, Sigma) and either control goat IgG or an agonist anti-mouse TIM-3 antibody (RnD Systems, 15 ug/ml) for 2 or 16 hours. The anti-TIM-3 samples were labeled by Cy5 and they were compared to the Cy3-labeled, goat IgG controls in a dual-color, paired experimental setup. The Agilent Whole Mouse Genome 4x44K expression microarray kit and Dual-Color Protocol version 5.5 were used in the experiments.
2009-10-15 | E-GEOD-14438 | biostudies-arrayexpress
Project description:TIM-3 is known to be expressed on dendritic cells, monocytes, melanoma cells, mast cells and on activated Th1 cells. In activated Th1 cells, stimulating TIM-3 by one of its ligands, galectin-9, leads to apoptosis and thus it plays a central role in terminating Th1-type immune responses. Interestingly, in IgE/antigen-activated mast cells TIM-3 enhances the production of IL-13 and IL-4. To get a more complete picture about the gene expression changes induced by TIM-3 in mast cells, in vitro differentiated mouse immature mast cells were stimulated by an agonist anti-TIM-3 antibody and IgE-sensitized mouse immature mast cells were activated by antigen and an agonist anti-TIM-3 antibody for 2 or 16 hours (overnight).
2009-10-01 | GSE14438 | GEO
Project description:TIM-3 on myeloid cells promotes pulmonary inflammation through increased production of galectin-3
| PRJNA1118218 | ENA
Project description:Hyperactive angiogenesis contributes to the immunosuppressive microenvironment important for immunotherapy, and LGALS1-encoed galectin-1 can trigger vascular signaling programs and mediate anti-angiogenic treatment response. However, the mechanism of galectin-1 regulation of angiogenesis is poorly understood. Previous mRNA interactome studies suggested that galectin-1 associated with mRNAs. In this study, we applied the iRIP-seq methodology, an unbiased genome-wide approach to study the RNA binding profiles of galectin-1. The results demonstrate that galectin-1 interacted with a large population of mRNAs with a preferred location towards stop codon, and preferred motifs of UGCA/UGGA and GAGCAG motifs. Galectin-1-bound mRNAs are enriched in cell cycle control and diverse basic biological processes, including its previously reported protein targets H-Ras and also T cell receptors TLR6. Glectin-1 significantly binds to genes in angiogenesis, which included the key pro-angiogenic growth factor VEGFA, angiogenic regulators EGR1 and LAMA5, suggesting that galectin-1 may regulate via its mRNA binding activity. The presented results uncover an previously unrecognized mRNA binding activity of galectin-1; further pursue of this activity could lead to knowledge important for developing therapeutic strategies against cancer and other diseases involved in aberrant angiogenesis.
2021-10-14 | GSE147565 | GEO
Project description:BackgroundT cell immunoglobulin and mucin-domain containing-3 (TIM-3) is a cell surface molecule that was first discovered on T cells. However, recent studies revealed that it is also highly expressed in acute myeloid leukemia (AML) cells and it is related to AML progression. As, Glutamine appears to play a prominent role in malignant tumor progression, especially in their myeloid group, therefore, in this study we aimed to evaluate the relation between TIM-3/Galectin-9 axis and glutamine metabolism in two types of AML cell lines, HL-60 and THP-1.MethodsCell lines were cultured in RPMI 1640 which supplemented with 10% FBS and 1% antibiotics. 24, 48, and 72 h after addition of recombinant Galectin-9 (Gal-9), RT-qPCR analysis, RP-HPLC and gas chromatography techniques were performed to evaluate the expression of glutaminase (GLS), glutamate dehydrogenase (GDH) enzymes, concentration of metabolites; Glutamate (Glu) and alpha-ketoglutarate (α-KG) in glutaminolysis pathway, respectively. Western blotting and MTT assay were used to detect expression of mammalian target of rapamycin complex (mTORC) as signaling factor, GLS protein and cell proliferation rate, respectively.ResultsThe most mRNA expression of GLS and GDH in HL-60 cells was seen at 72 h after Gal-9 treatment (p = 0.001, p = 0.0001) and in THP-1 cell line was observed at 24 h after Gal-9 addition (p = 0.001, p = 0.0001). The most mTORC and GLS protein expression in HL-60 and THP-1 cells was observed at 72 and 24 h after Gal-9 treatment (p = 0.0001), respectively. MTT assay revealed that Gal-9 could promote cell proliferation rate in both cell lines (p = 0.001). Glu concentration in HL-60 and α-KG concentration in both HL-60 (p = 0.03) and THP-1 (p = 0.0001) cell lines had a decreasing trend. But, Glu concentration had an increasing trend in THP-1 cell line (p = 0.0001).ConclusionTaken together, this study suggests TIM-3/Gal-9 interaction could promote glutamine metabolism in HL-60 and THP-1 cells and resulting in AML development.
| S-EPMC10809689 | biostudies-literature