Ontology highlight
ABSTRACT:
PROVIDER: PRJNA896905 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22141016_1.fastq.gz | Fastqsanger.gz | |||
| SRR22141016_2.fastq.gz | Fastqsanger.gz | |||
| SRR22141017_1.fastq.gz | Fastqsanger.gz | |||
| SRR22141017_2.fastq.gz | Fastqsanger.gz | |||
| SRR22141018_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 16 |
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Project description:This randomized phase I/II clinical trial is studying the side effects and best dose of gamma-secretase/notch signalling pathway inhibitor RO4929097 when given together with vismodegib and to see how well they work in treating patients with advanced or metastatic sarcoma. Vismodegib may slow the growth of tumor cells. Gamma-secretase/notch signalling pathway inhibitor RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving vismodegib together with gamma-secretase/notch signalling pathway inhibitor RO4929097 may be an effective treatment for sarcoma.
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Project description:Interferon-gamma (IFN-γ) is a key regulator of immune responses. A hallmark of the IFN-γ response is inducible nitric oxide (NO) production, driven primarily by nitric oxide synthase 2 (NOS2). In this study, we investigated the influence of NO on the IFN-γ-induced transcriptomic and metabolic changes in the RAW 264.7 macrophage cell line. IFN-γ activation led to NO-dependent lactate production and lower cell survival. Bulk RNA sequencing analysis identified genes differentially expressed by IFN-γ that were either NO-independent or NO-dependent. Inhibition of NO modulated a minor subset of the transcriptome, notably affecting Klf6 (a tumor suppressor) and Zfp36 (a regulator of pro-inflammatory cytokines). Both Klf6 and Zfp36 correlatively showed high expression in most cancers. The PPI network exhibited dense clustering with scale-free and small-world properties, identifying Stat1, Irf7, Irf1, Cxcl10, and Isg15 as top five hubs. The top IFN-γ signalling genes exhibited deficient expression in the brain but were highly expressed in lung, spleen, and EBV-transformed lymphocytes. Gene-disease associations linked the IFN-g-regulated genes to immunodeficiencies, chronic inflammatory responses and malignancies. Interestingly, IFN-γ upregulated genes were involved in nicotinamide metabolism, suggesting a transcriptional basis for modulation of metabolic pathways. This novel aspect was experimentally tested to show that IFN-γ induced NAD amounts. Importantly, the inhibition of purine nucleoside phosphorylase (using Forodesine hydrochloride) which is involved in the endogenous pathway for NAD generation, lowered IFN-γ induced nitrite and increased cell survival in vitro. Functionally, enriched nicotinamide metabolism by IFN-g may regulate inflammatory responses and the implications of our findings are discussed.
2025-01-18 | GSE286915 | GEO
Project description:Natural killer (NK) cells are lymphocytes of the innate immune system that are involved in controlling tumors or microbial infections through the production of interferon gamma (IFN-γ). Granulocyte-colony stimulating factor (G-CSF) inhibits IFN-γ secretion by NK cells, but the mechanism underlying this effect remains unclear. Here, by comparing the multi-omics profiles of human NK cells before and after in vivo G-CSF treatment, we identified a pathway that was activated in response to G-CSF treatment, which suppressed IFN-γ secretion in NK cells. Specifically, our integrative genomic strategy revealed glucocorticoid receptor (GR) activation in NK cells that mediated the genomic response to G-CSF treatment. Activated GRs can inhibit secretion of IFN-γ by promoting interactions between suppressor of cytokine signaling 1 (SOCS1) promoter and enhancer, as well as increase the expression of SOCS1. Experiments in mice confirmed that G-CSF in vivo treatment significantly down-regulated IFN-γ secretion and up-regulated GR and SOCS1 expression in NK cells. In addition, GR blockade (RU486) significantly reversed the effects of G-CSF, demonstrating that GR up-regulates SOCS1 and inhibits the production of IFN-γ by NK cells.
2022-09-14 | GSE205824 | GEO
Project description:Natural killer (NK) cells are lymphocytes of the innate immune system that are involved in controlling tumors or microbial infections through the production of interferon gamma (IFN-γ). Granulocyte-colony stimulating factor (G-CSF) inhibits IFN-γ secretion by NK cells, but the mechanism underlying this effect remains unclear. Here, by comparing the multi-omics profiles of human NK cells before and after in vivo G-CSF treatment, we identified a pathway that was activated in response to G-CSF treatment, which suppressed IFN-γ secretion in NK cells. Specifically, our integrative genomic strategy revealed glucocorticoid receptor (GR) activation in NK cells that mediated the genomic response to G-CSF treatment. Activated GRs can inhibit secretion of IFN-γ by promoting interactions between suppressor of cytokine signaling 1 (SOCS1) promoter and enhancer, as well as increase the expression of SOCS1. Experiments in mice confirmed that G-CSF in vivo treatment significantly down-regulated IFN-γ secretion and up-regulated GR and SOCS1 expression in NK cells. In addition, GR blockade (RU486) significantly reversed the effects of G-CSF, demonstrating that GR up-regulates SOCS1 and inhibits the production of IFN-γ by NK cells.
2022-09-14 | GSE205821 | GEO
Project description:Natural killer (NK) cells are lymphocytes of the innate immune system that are involved in controlling tumors or microbial infections through the production of interferon gamma (IFN-γ). Granulocyte-colony stimulating factor (G-CSF) inhibits IFN-γ secretion by NK cells, but the mechanism underlying this effect remains unclear. Here, by comparing the multi-omics profiles of human NK cells before and after in vivo G-CSF treatment, we identified a pathway that was activated in response to G-CSF treatment, which suppressed IFN-γ secretion in NK cells. Specifically, our integrative genomic strategy revealed glucocorticoid receptor (GR) activation in NK cells that mediated the genomic response to G-CSF treatment. Activated GRs can inhibit secretion of IFN-γ by promoting interactions between suppressor of cytokine signaling 1 (SOCS1) promoter and enhancer, as well as increase the expression of SOCS1. Experiments in mice confirmed that G-CSF in vivo treatment significantly down-regulated IFN-γ secretion and up-regulated GR and SOCS1 expression in NK cells. In addition, GR blockade (RU486) significantly reversed the effects of G-CSF, demonstrating that GR up-regulates SOCS1 and inhibits the production of IFN-γ by NK cells.
2022-09-14 | GSE205823 | GEO
Project description:Natural killer (NK) cells are lymphocytes of the innate immune system that are involved in controlling tumors or microbial infections through the production of interferon gamma (IFN-γ). Granulocyte-colony stimulating factor (G-CSF) inhibits IFN-γ secretion by NK cells, but the mechanism underlying this effect remains unclear. Here, by comparing the multi-omics profiles of human NK cells before and after in vivo G-CSF treatment, we identified a pathway that was activated in response to G-CSF treatment, which suppressed IFN-γ secretion in NK cells. Specifically, our integrative genomic strategy revealed glucocorticoid receptor (GR) activation in NK cells that mediated the genomic response to G-CSF treatment. Activated GRs can inhibit secretion of IFN-γ by promoting interactions between suppressor of cytokine signaling 1 (SOCS1) promoter and enhancer, as well as increase the expression of SOCS1. Experiments in mice confirmed that G-CSF in vivo treatment significantly down-regulated IFN-γ secretion and up-regulated GR and SOCS1 expression in NK cells. In addition, GR blockade (RU486) significantly reversed the effects of G-CSF, demonstrating that GR up-regulates SOCS1 and inhibits the production of IFN-γ by NK cells.
2022-09-14 | GSE205822 | GEO
Project description:The purpose of the study was to investigate the effect of IFN-γ on transcriptomic profile of differentiating mouse C2C12 myogenic cells. Global gene expression was evaluated using the oligonucleotide whole mouse genome microarrays and was validated with real-time PCR method. Exogenous IFN-γ (1 ng/ml) increased myoblast proliferation, but decreased cell viability, the fusion index and the cellular content of myosin heavy chain, MyHC in C2C12 cultures on the 3rd day of differentiation. IFN-γ up-regulated genes were mainly involved in biological processes such as: cell cycle, regulation of cell proliferation, programmed cell death, inflammatory, vasculature development, regulation of cytokine, transmembrane receptor protein tyrosine kinase signaling pathway, and chemotaxis, whereas down-regulated genes contributed mainly to: regulation of transcription, cell-cell signaling, nitrogen compound biosynthetic process, transmembrane receptor protein ser/thr protein kinase signaling pathway, and regulation of Wnt receptor signaling pathway. IFN-γ up-regulated the expression of cytokines/growth factors controlling cell proliferation (Cxcl10, Il15, Ccl2, Fgf7, Figf, Csf1, Vegfc, Hgf). Moreover, IFN-γ: i) down-regulated genes encoding factors that are anabolic for muscle cells (Fst, Igf-1); ii) inhibited pro-myogenic transcription (via Mef2a, Nfkb1, and Pparg); iii) decreased expression of genes controlling cell adhesion and sarcolemma/cytoskeleton organization; and iv) activated the proteolytic pathways: proteasomes and catepsins, leading to protein degradation and impaired myotube growth. Our data suggest that the effect of IFN-γ on mygenesis is, at least partly, associated with the regulation of muscle cell secretom at the transcriptional level. To whom the correspondence should be addressed: Dr K. Grzelkowska-Kowalczyk; e-mail: k_grzel_kow@poczta.fm, tel/fax: (48 22) 847 24 52
2014-02-05 | GSE53392 | GEO
Project description:Qi2013 - IL-6 and IFN crosstalk model
This model
[BIOMD0000000544]
describes the crosstalk between IFN-gamma and IL-6 induced
signalling; it aims to outline mechanisms and factors that may
control the interaction between both signalling pathways,
discussing a role of heterodimer formation in signalling
dysfunction.
To account for the possibility of different IFNR and gp130
binding sites for STAT1 and STAT3, model 1
[BIOMD0000000543]
assumes that there is no competition between STAT1 and STAT3 for
the receptor complexes (includes two extra reactions).
The reverse of this is true in model 2
[BIOMD0000000544]
where it generally is assumed that there is competition between
STAT1 and STAT3 for the receptor complexes.
This model is described in the article:
Elucidating the crosstalk
mechanism between IFN-gamma and IL-6 via mathematical
modelling.
Qi YF, Huang YX, Wang HY, Zhang Y,
Bao YL, Sun LG, Wu Y, Yu CL, Song ZB, Zheng LH, Sun Y, Wang GN,
Li YX.
BMC Bioinformatics 2013; 14: 41
Abstract:
BACKGROUND: Interferon-gamma (IFN-gamma) and interleukin-6
(IL-6) are multifunctional cytokines that regulate immune
responses, cell proliferation, and tumour development and
progression, which frequently have functionally opposing roles.
The cellular responses to both cytokines are activated via the
Janus kinase/signal transducer and activator of transcription
(JAK/STAT) pathway. During the past 10 years, the crosstalk
mechanism between the IFN-gamma and IL-6 pathways has been
studied widely and several biological hypotheses have been
proposed, but the kinetics and detailed crosstalk mechanism
remain unclear. RESULTS: Using established mathematical models
and new experimental observations of the crosstalk between the
IFN-gamma and IL-6 pathways, we constructed a new crosstalk
model that considers three possible crosstalk levels: (1) the
competition between STAT1 and STAT3 for common receptor docking
sites; (2) the mutual negative regulation between SOCS1 and
SOCS3; and (3) the negative regulatory effects of the formation
of STAT1/3 heterodimers. A number of simulations were tested to
explore the consequences of cross-regulation between the two
pathways. The simulation results agreed well with the
experimental data, thereby demonstrating the effectiveness and
correctness of the model. CONCLUSION: In this study, we
developed a crosstalk model of the IFN-gamma and IL-6 pathways
to theoretically investigate their cross-regulation mechanism.
The simulation experiments showed the importance of the three
crosstalk levels between the two pathways. In particular, the
unbalanced competition between STAT1 and STAT3 for IFNR and
gp130 led to preferential activation of IFN-gamma and IL-6,
while at the same time the formation of STAT1/3 heterodimers
enhanced preferential signal transduction by sequestering a
fraction of the activated STATs. The model provided a good
explanation of the experimental observations and provided
insights that may inform further research to facilitate a
better understanding of the cross-regulation mechanism between
the two pathways.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000544.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2024-09-02 | BIOMD0000000544 | BioModels
Project description:Qi2013 - IL-6 and IFN crosstalk model
(non-competitive)
This model
[BIOMD0000000543]
describes the crosstalk between IFN-gamma and IL-6 induced
signalling; it aims to outline mechanisms and factors that may
control the interaction between both signalling pathways,
discussing a role of heterodimer formation in signalling
dysfunction.
To account for the possibility of different IFNR and gp130
binding sites for STAT1 and STAT3, model 1
[BIOMD0000000543]
assumes that there is no competition between STAT1 and STAT3 for
the receptor complexes (includes two extra reactions).
The reverse of this is true in model 2
[BIOMD0000000544]
where it generally is assumed that there is competition between
STAT1 and STAT3 for the receptor complexes.
This model is described in the article:
Elucidating the crosstalk
mechanism between IFN-gamma and IL-6 via mathematical
modelling.
Qi YF, Huang YX, Wang HY, Zhang Y,
Bao YL, Sun LG, Wu Y, Yu CL, Song ZB, Zheng LH, Sun Y, Wang GN,
Li YX.
BMC Bioinformatics 2013; 14: 41
Abstract:
BACKGROUND: Interferon-gamma (IFN-gamma) and interleukin-6
(IL-6) are multifunctional cytokines that regulate immune
responses, cell proliferation, and tumour development and
progression, which frequently have functionally opposing roles.
The cellular responses to both cytokines are activated via the
Janus kinase/signal transducer and activator of transcription
(JAK/STAT) pathway. During the past 10 years, the crosstalk
mechanism between the IFN-gamma and IL-6 pathways has been
studied widely and several biological hypotheses have been
proposed, but the kinetics and detailed crosstalk mechanism
remain unclear. RESULTS: Using established mathematical models
and new experimental observations of the crosstalk between the
IFN-gamma and IL-6 pathways, we constructed a new crosstalk
model that considers three possible crosstalk levels: (1) the
competition between STAT1 and STAT3 for common receptor docking
sites; (2) the mutual negative regulation between SOCS1 and
SOCS3; and (3) the negative regulatory effects of the formation
of STAT1/3 heterodimers. A number of simulations were tested to
explore the consequences of cross-regulation between the two
pathways. The simulation results agreed well with the
experimental data, thereby demonstrating the effectiveness and
correctness of the model. CONCLUSION: In this study, we
developed a crosstalk model of the IFN-gamma and IL-6 pathways
to theoretically investigate their cross-regulation mechanism.
The simulation experiments showed the importance of the three
crosstalk levels between the two pathways. In particular, the
unbalanced competition between STAT1 and STAT3 for IFNR and
gp130 led to preferential activation of IFN-gamma and IL-6,
while at the same time the formation of STAT1/3 heterodimers
enhanced preferential signal transduction by sequestering a
fraction of the activated STATs. The model provided a good
explanation of the experimental observations and provided
insights that may inform further research to facilitate a
better understanding of the cross-regulation mechanism between
the two pathways.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000543.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2024-09-02 | BIOMD0000000543 | BioModels
Project description:PGE2 is a major mediator of inflammation and is present at high concentrations in the synovial fluid of rheumatoid arthritis (RA) patients. PGE2, acting through the EP4 receptor, has both pro- and anti-inflammatory roles in vivo. To shed light on this dual role of PGE2, we investigated its effects in whole blood and in primary human fibroblast-like synoviocytes. Gene expression analysis in human leukocytes, confirmed at the protein level, revealed an EP4-dependent inhibition of the expression of genes involved in the IFN-gamma activation pathway, including IFN-gamma itself. This effect of the PGE2/EP4 axis on IFN-gamma is a reciprocal phenomenon since IFN-gamma blocks PGE2 release and blocks EP receptor expression. The mutually antagonistic relationship between IFN-gamma and PGE2 extends to downstream cytokine- and chemokine-release; PGE2 counters the effects of IFN-gamma, on the release of IP-10, IL-8, TNFalpha and IL-1beta. To gain further insight into IFN-gamma-mediated cellular events in rheumatoid arthritis, we assessed the effects of IFN-gamma on gene expression in fibroblast-like synoviocytes. We observed an IFN-gamma-dependent up-regulation of macrophage-attracting chemokines, and down-regulation of metalloprotease expression. These results suggest the existence of a mutually antagonistic relationship between PGE2 and IFN-gamma which may represent a fundamental mechanism of immune control in diseases such as RA. For details, see Mathieu MC et al, EJI, issue 7, 2008
2008-05-29 | E-GEOD-11575 | biostudies-arrayexpress