Response of several cell lines originated from liver, skin and colon to stimulation by IFNg, hyper-IL6, IL27 and OSM, investigated at microRNA level
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Iris Behrmann
PROVIDER: E-MTAB-9118 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:In this study 6 cell lines originated from liver, skin and colon tumours as well as 3 non-tumour cell lines from the same organs were profiled with and without stimulation by 4 cytokines: IFNg, hyper-IL6, IL27 and OSM. The main objective was investigation of downstream effects of the stimulation if these cancer cell lines as well as in healthy tissues.
2018-10-01 | E-MTAB-6080 | biostudies-arrayexpress
Project description:Interleukin-27 (IL27) is a type-I-cytokine of the IL6/IL12 family predominantly secreted by activated macrophages and dendritic cells. Best understood are the effects of IL27 on immune cells where it has been described to have pro- or anti-inflammatory properties, either promoting TH1 responses or suppressing TH1 and TH2 responses. The action on other cell types is less well studied. In the liver, IL27 expression was observed to be upregulated in patients with hepatitis B, and sera of hepatocellular carcinoma (HCC) patients contain significantly elevated levels of IL27 compared to healthy controls or patients with hepatitis and/or liver cirrhosis. We previously reported interferon-gamma-like antiviral activity of IL27 in hepatic cells. Here we further studied the effects of IL27 on HCC cells in comparison to other cytokines. We were especially interested in the relevance of the IL27-induced STAT3 activation. Thus we compared its response with those induced by IFNg (STAT1-dominated response) or IL6-type cytokines (IL6, Hyper-IL6 or OSM) (STAT3-dominated response). We find that in hepatocytes, IL27 induces an IFNg-like, STAT1-dependent transcriptional response, but we do not find an effective STAT3-dependent response. The availability of STAT1 seems critical in the shaping of the IL27 response, as the siRNA knock-down of STAT1 revealed its ability to induce the acute-phase protein gamma-fibrinogen, a typical IL6 family characteristic. Moreover, we describe a crosstalk between the signaling of IL6-type cytokines and IL27: responses to the gp130-engaging cytokine IL27 (but not those to IFNs) can be inhibited by IL6-type cytokine pre-stimulation, likely by a SOCS3-mediated mechanism. This experiment represents microarray analysis of three hepatocellular carcinoma cell lines treated with IL-27, IFNg, hyper-IL6 or OSM in combination with shRNA knockdown of STAT3.
2017-07-05 | E-MTAB-4570 | biostudies-arrayexpress
Project description:In this study, primary health liver cells obtained from patients with colon cancer and liver metastasis were stimulated with hyper-IL-6 for 6, 24, 48 and 72 h or kept untreated. Both mRNA and miRNA levels were characterized (this is miRNA dataset).
2019-02-28 | E-MTAB-6572 | biostudies-arrayexpress
Project description:In this study, two hepatic cell lines were stimulated with hyper-IL-6 for 6, 24, 48 and 72 h or kept untreated.
2022-06-30 | E-MTAB-10646 | biostudies-arrayexpress
Project description:Defects in stress responses are important contributors in many chronic conditions including cancer, cardiovascular disease, diabetes, and obesity-driven pathologies like non-alcoholic steatohepatitis (NASH). Specifically, endoplasmic reticulum (ER) stress is linked with these pathologies and control of ER stress can ameliorate tissue damage. MicroRNAs have a critical role in regulating diverse stress responses including ER stress. Here we show that miR-494-3p plays a functional role during ER stress. ER stress inducers (tunicamycin and thapsigargin) robustly increase the expression of miR-494 in vitro in an ATF6 dependent manner. Surprisingly, miR-494 pretreatment dampens the induction and magnitude of ER stress in response to tunicamycin in endothelial cells. Conversely, inhibition of miR-494 increases ER stress de novo and amplifies the effects of ER stress inducers. Using Mass Spectrometry (TMT-MS) we identified many proteins that are downregulated by both tunicamycin and miR-494 in cultured human umbilical vein endothelial cells (HUVECs). Among these, we found 6 transcripts which harbor a putative miR-494 binding site. Our data indicates that ER stress driven miR-494 may act in a feedback inhibitory loop to dampen downstream ER stress signaling. We propose that RNA-based approaches targeting miR-494 or its targets may be attractive candidates for inhibiting ER stress dependent pathologies in human disease.
2021-09-09 | PXD019992 | Pride
Project description:Metastasis is a major cause of mortality, and remains a final frontier in the search for a cure for cancer. While there has been much research on the ‘seed’ (metastatic tumor cells) and the ‘soil’ (colonized host tissue), interactions between metastatic cancer cells and stromal endothelial cells, which occur at multiple stages during metastasis, are less well understood. Here we report a dynamic regulation of the endothelium by cancer cells through the formation of nanoscale intercellular membrane bridges, which act as physical conduits for intercellular communication in vitro and in vivo, including horizontal transfer of microRNAs (miRNA). The communication between the tumor cell and the endothelium upregulates markers associated with pathological endothelium, which is reversed by pharmacological inhibition of these nanoscale conduits. These results lead us to define the notion of “metastatic hijack”: cancer cell-induced transformation of healthy endothelium into pathological endothelium via horizontal communication through the nanoscale conduits. Pharmacological perturbation of these nanoscale membrane bridges decreases metastatic foci in syngeneic- and human xenograft-breast cancer models. Targeting the formation of these nanoscale membrane bridges may potentially emerge as a new therapeutic opportunity in the management of metastatic cancer. A miRNA microarray was used to evaluate the transport of endogenous microRNAs. The intercellular transfer-ve and intercellular transfer+ve samples were sorted from the same endothelial cell population with the only difference being the occurrence of intercellular transport. The heat map shows potential miRNA candidates for exogenous transfer on two independent biological replicates. These miRNA candidates were significantly up-regulated in the cells receiving transfer of intercellular contents. HUVECs that were not exposed to cancer cells were used as a baseline control.
2015-09-04 | E-GEOD-72679 | biostudies-arrayexpress
Project description:Exosomes were isolated by differential centrifugation from the fusion negative human embryonal rhabdomyosarcoma (ERMS) cell lines (JR1, Rh36, and RD) and fusion positive alveolar RMS (ARMS) cell lines (Rh30 and Rh41) and characterized by western blot for exosomal markers. miRNA content of the RMS-derived exosomes was determined using the Affymetrix GeneChip miRNA 3.0 array and analyzed to specify differentially deregulated (either enriched or depleted) miRNA relative to cellular miRNA from the respective ERMS and ARMS cell lines. Characterization of the miRNA content of RMS exosome is needed to better understand the mechanism by which these particles exert their physiologic effects, notably on proliferation, migration, invasion, and metastasis.
2016-12-01 | E-MTAB-5321 | biostudies-arrayexpress
Project description:In this study, primary healthy liver cells obtained from patients with colon cancer and liver metastasis were stimulated with hyper-IL-6 for 6, 24, 48 and 72 h or kept untreated. Both mRNA and miRNA levels were characterized (this is mRNA dataset).
2019-02-28 | E-MTAB-6571 | biostudies-arrayexpress
Project description:Interleukin-6 (IL-6) plays an important role in progressive bone loss in rheumatoid arthritis (RA). However, the molecular mechanisms through which IL-6 propels RA synovial fibroblasts (RASFs) to contribute to bone loss are not fully understood. In the present study, we investigated the effects of IL-6 and IL-6 receptor (IL-6/IL-6R induced trans-signaling in human RASFs. Treatment of human RASFs with IL-6 and IL-6 receptor (IL-6/IL-6R, 100 ng/ml each) alone or in combination with M-CSF (2 ng/ml) and RANKL (10 ng/ml) for 12 days resulted in the phenotypic changes to osteoclast-like features as determined by increase in TRAP staining and enhanced pit formation by ~3-fold in bone resorption assay in vitro. IL-6/IL-6R induced a dose-dependent increase in the expression of transcription factor Ets2 and enhanced its nuclear translocation in human RASFs. Interestingly, the untargeted proteomics analysis of the conditioned media from IL6/IL6R activated RASFs using Mass-Spectrometry (MS) technique and Trans-Proteomic Pipeline tool showed the production of 113 analytes unique to IL-6/IL-6R stimulation. Further analysis of the proteomics data using STRING database for pathway analysis showed the impact of IL-6/IL-6R on immunometabolic reprogramming of human RASFs towards osteoclast-like phenotype, which was partly mediated through Ets2. These preliminary studies identified a novel role of IL-6/IL-6R-mediated trans signaling in the metabolic reprogramming in RASFs that could potentially be targeted by inhibiting Ets2 to limit their role in bone resorption in RA.
2021-11-02 | PXD028374 | Pride
Project description:Background & Aims: The association between chronic inflammation and gastric carcinogenesis is well established, but it is not clear how immune cells and cytokines regulate this process. We investigated the role of interleukin 27 (IL27) in the development of gastric atrophy, hyperplasia, and metaplasia (preneoplastic lesions associated with inflammation-induced gastric cancer) in mice with autoimmune gastritis. Methods: We performed studies with TxA23 mice (control mice), which express a T-cell receptor against the H+/K+ adenosine triphosphatase α chain and develop autoimmune gastritis, and TxA23xEbi3-/- mice, which develop gastritis but do not express IL27. In some experiments, mice were given high-dose tamoxifen to induce parietal cell atrophy and spasmolytic polypeptide-expressing metaplasia (SPEM). Recombinant IL27 was administered to mice with mini osmotic pumps. Stomachs were collected and analyzed by histopathology and immunofluorescence; we used flow cytometry to measure IL27 and identify immune cells that secrete IL27 in the gastric mucosa. Single-cell RNA sequencing was performed on immune cells that infiltrated stomach tissues. Results: We identified IL27-secreting macrophages and dendritic cell in the corpus of mice with chronic gastritis (TxA23 mice). Mice deficient in IL27 developed more severe gastritis, atrophy, and SPEM than control mice. Administration of recombinant IL27 significantly reduced the severity of inflammation, atrophy, and SPEM in mice with gastritis. Single-cell RNA sequencing showed that IL27 acted almost exclusively on stomach-infiltrating CD4+ T cells to suppress expression of inflammatory genes. Conclusions: In studies of mice with autoimmune gastritis, we found that IL27 is an inhibitor of gastritis and SPEM, suppressing CD4+ T-cell–mediated inflammation in the gastric mucosa.
2024-10-01 | GSE278552 | GEO