Project description:Mice bone marrow cells induced dendritic cells were treated with a p38 inhibitor, we used Microgenearry to analyze the dendritic cell-related gene expression, which was induced by a p38 inhibitor. Mice were treated with CAR-T cells with or without p38 inhibitor treatment, we used Microgenearry to analyze the dendritic cell-related gene expression in the tumor environment. Tumor tissues (~100 mg/mouse, 12 days after ACT) were harvested and total RNA was extracted with the RNeasy Mini kit (Qiagen).
Project description:U-2 OS (human osteosarcoma cell line) were treated with ZM447439 (an aurora kinase inhibitor), SB202190 (a p38 inhibitor) or ZM447439+SB202190 and resulting changes in gene expression were profiled.
Project description:In order to identify the effects of JNK inhibitor or p38 Inhibitor on the transcriptome of ATP7B H1069Q-overexpressing liver cells, we performed RNAseq experiments
Project description:Cells have the ability to respond and adapt to environmental changes through the activation of stress-activated protein kinases (SAPKs). Although it has been shown that p38 SAPK signalling participates in the regulation of gene transcription, there is not a comprehensive genome-wide transcription study reported to date describing neither the role of the p38 SAPK on the immediate response to stress and its kinetics nor a comparative vision of the genes that respond to different stimuli that activate the p38 SAPK. Here, we report a whole genome microarray analyses on wild type mouse embryonic fibroblasts (MEFs) treated with different p38 SAPK activators, namely the physiological cytokine TNF alpha, the protein synthesis inhibitor antibiotic anisomycin and osmostress. In addition, we have analysed the contribution of p38 alpha the major isoform of p38 present in MEF cells, in the overall transcription in response to those stimuli by both, the inhibition of p38 SAPK by using a chemical inhibitor (SB203580) and the use of p38 alpha knock out MEFs. Furthermore, we have analysed the kinetics of the gene expression response to osmostress by the p38 SAPK. Two samples have been analysed; wild type Mouse embryonic fibroblast (WT-MEFs) and MAPK p38alfa knock out MEFs (KO-MEFs) respectively treated with 11 and 4 different treatments. Each experiment was performed in duplicate and referenced to a pool of two non-treated WT MEFs.
Project description:Cells have the ability to respond and adapt to environmental changes through the activation of stress-activated protein kinases (SAPKs). Although it has been shown that p38 SAPK signalling participates in the regulation of gene transcription, there is not a comprehensive genome-wide transcription study reported to date describing neither the role of the p38 SAPK on the immediate response to stress and its kinetics nor a comparative vision of the genes that respond to different stimuli that activate the p38 SAPK. Here, we report a whole genome microarray analyses on wild type mouse embryonic fibroblasts (MEFs) treated with different p38 SAPK activators, namely the physiological cytokine TNF alpha, the protein synthesis inhibitor antibiotic anisomycin and osmostress. In addition, we have analysed the contribution of p38 alpha the major isoform of p38 present in MEF cells, in the overall transcription in response to those stimuli by both, the inhibition of p38 SAPK by using a chemical inhibitor (SB203580) and the use of p38 alpha knock out MEFs. Furthermore, we have analysed the kinetics of the gene expression response to osmostress by the p38 SAPK.
Project description:Cutaneous T-Cell Lymphomas (CTCL) represent a group of hematopoietic malignancies that home to the skin and have no known molecular basis for disease pathogenesis. Sézary syndrome (SS) is the leukemic variant of CTCL. Currently, CTCL is incurable, highlighting the need for new therapeutic modalities. We have previously observed that combined small-molecule inhibition of protein kinase C (PKC) β and glycogen synthase kinase 3 (GSK3) causes synergistic apoptosis in CTCL cell lines and patient cells. Through microarray analysis of a SS cell line, we surveyed global gene expression following combined PKCβ-GSK3 treatment to elucidate therapeutic targets responsible for cell death. Clinically relevant targets were defined as genes differentially expressed in SS patients that were modulated by combination-drug treatment of SS cells. Gene set enrichment analysis uncovered candidate genes enriched for an immune cell signature, specifically the T-cell receptor and MAPK signaling pathways. Further analysis identified p38 as a potential therapeutic target that is over-expressed in SS patients and decreased by synergistic-inhibitor treatment. This target was verified through small-molecule inhibition of p38 leading to cell death in both SS cell lines and patient cells. These data establish p38 as a new SS biomarker and potential therapeutic target for the treatment of CTCL. Hut78 cells were treated with 4μM Enzastaurin, 5μM AR-A014418, 4μM Enzastaurin & 5μM AR-A014418, DMSO, or no treatment for three days. RNA was extracted and hybridized to Illumina microarrays.
Project description:Cutaneous T-Cell Lymphomas (CTCL) represent a group of hematopoietic malignancies that home to the skin and have no known molecular basis for disease pathogenesis. Sézary syndrome (SS) is the leukemic variant of CTCL. Currently, CTCL is incurable, highlighting the need for new therapeutic modalities. We have previously observed that combined small-molecule inhibition of protein kinase C (PKC) β and glycogen synthase kinase 3 (GSK3) causes synergistic apoptosis in CTCL cell lines and patient cells. Through microarray analysis of a SS cell line, we surveyed global gene expression following combined PKCβ-GSK3 treatment to elucidate therapeutic targets responsible for cell death. Clinically relevant targets were defined as genes differentially expressed in SS patients that were modulated by combination-drug treatment of SS cells. Gene set enrichment analysis uncovered candidate genes enriched for an immune cell signature, specifically the T-cell receptor and MAPK signaling pathways. Further analysis identified p38 as a potential therapeutic target that is over-expressed in SS patients and decreased by synergistic-inhibitor treatment. This target was verified through small-molecule inhibition of p38 leading to cell death in both SS cell lines and patient cells. These data establish p38 as a new SS biomarker and potential therapeutic target for the treatment of CTCL.
Project description:Human monocytic THP-1 cells were exposed to HIV envelope protein gp120 or bacterial LPS in the presence and absence of a pharmacological inhibitor of the p38 mitogen-activated protein kinase (MAPK) for 4 and 24 hours. A microarray analysis was performed in order to assess differential gene expression at the RNA level.