Transcriptome analysis of J774A.1 macrophages undergoing amino acid deprivation
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE14293 | GEO | 2009/02/05
SECONDARY ACCESSION(S): PRJNA111291
REPOSITORIES: GEO
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Project description:Phagocytosis represents a mechanism used by macrophages to remove pathogens and cellular debris. Recent evidence suggested that amino acid or glucose deprivation may cause an increase in phagocytosis of heat-inactivated Escherichia coli and Staphylococcus aureus by macrophages, but not the uptake of platelets, apoptotic cells or beads. Increased phagocytosis of bacteria could be blocked by phagocytosis inhibitors and depended on p38 MAP kinase activity. To examine potentially important downstream pathways linked to EBSS-induced starvation and p38 MAP kinase activation, a full genome microarray representing over 41,000 mouse genes or transcripts was probed with cDNA isolated from J774A.1 macrophages that were treated with EBSS, EBSS supplemented with the p38 inhibitor SB202190 or control medium supplemented with 10% fetal bovine serum. Keywords: autophagy, heterophagy, p38 MAP kinase, scavenger receptor A, starvation Prior to RNA isolation, J774A.1 macrophages were incubated in RPMI 1640 medium supplemented with (i) 10% fetal bovine serum, (ii) Earleâs Balanced Salt Solution (EBSS) or (iii) EBSS supplemented with 10 µM SB202190 for 6 hours.
2010-05-06 | E-GEOD-14293 | biostudies-arrayexpress
Project description:Highly pathogenic avian influenza viruses (HPAIV) induce severe inflammation in poultry and men. There is still an ongoing threat that these viruses may acquire the capability to freely spread as novel pandemic virus strains that may cause major morbidity and mortality. One characteristic of HPAIV infections is the induction of a cytokine burst that strongly contributes to viral pathogenicity. It has been suggested, that this cytokine overexpression is an intrinsic feature of infected cells and involves hyperinduction of p38 mitogen activated protein kinase (MAPK). Here we investigate the role of MAPK p38 signaling in the antiviral response against HPAIV in mice as well as in endothelial cells, the latter a primary source for cytokines during systemic infections. Global gene expression profiling of HPAIV infected endothelial cells in the presence of the MAP kinase p38-specific inhibitor SB202190 revealed, that inhibition of MAPK p38 leads to reduced expression of interferon (IFN) and other cytokines after A/Thailand/1(KAN-1)/2004 (H5N1) and A/FPV/Bratislava/79 (H7N7) infection. Furthermore, the expression of interferon stimulated genes (ISGs) after treatment with IFN or conditioned media from HPAIV infected cells was decreased when the target cells were preincubated with SB202190. Finally, promoter analysis confirmed a direct impact of p38 MAPK on the IFN-enhanceosome and ISG-promoter activity. In vivo inhibition of MAP kinase p38 greatly diminishes virus induced cytokine expression concomitant with reduced viral titers, thereby protecting mice from lethal infection. These observations show, that MAPK p38 acts on two levels of the antiviral IFN response: Initially the kinase regulates IFN induction and at a later stage MAPK p38 controls IFN signaling and thereby expression of IFN-stimulated genes. Thus, inhibition of MAP kinase p38 may be an antiviral strategy that significantly protects mice from lethal influenza via suppression of overshooting cytokine expression. HUVEC were infected with FPV in the presence or absence of a p38 MAP kinase inhibitor
2013-05-31 | E-GEOD-40281 | biostudies-arrayexpress
Project description:Highly pathogenic avian influenza viruses (HPAIV) induce severe inflammation in poultry and men. There is still an ongoing threat that these viruses may acquire the capability to freely spread as novel pandemic virus strains that may cause major morbidity and mortality. One characteristic of HPAIV infections is the induction of a cytokine burst that strongly contributes to viral pathogenicity. It has been suggested, that this cytokine overexpression is an intrinsic feature of infected cells and involves hyperinduction of p38 mitogen activated protein kinase (MAPK). Here we investigate the role of MAPK p38 signaling in the antiviral response against HPAIV in mice as well as in endothelial cells, the latter a primary source for cytokines during systemic infections. Global gene expression profiling of HPAIV infected endothelial cells in the presence of the MAP kinase p38-specific inhibitor SB202190 revealed, that inhibition of MAPK p38 leads to reduced expression of interferon (IFN) and other cytokines after A/Thailand/1(KAN-1)/2004 (H5N1) and A/FPV/Bratislava/79 (H7N7) infection. Furthermore, the expression of interferon stimulated genes (ISGs) after treatment with IFN or conditioned media from HPAIV infected cells was decreased when the target cells were preincubated with SB202190. Finally, promoter analysis confirmed a direct impact of p38 MAPK on the IFN-enhanceosome and ISG-promoter activity. In vivo inhibition of MAP kinase p38 greatly diminishes virus induced cytokine expression concomitant with reduced viral titers, thereby protecting mice from lethal infection. These observations show, that MAPK p38 acts on two levels of the antiviral IFN response: Initially the kinase regulates IFN induction and at a later stage MAPK p38 controls IFN signaling and thereby expression of IFN-stimulated genes. Thus, inhibition of MAP kinase p38 may be an antiviral strategy that significantly protects mice from lethal influenza via suppression of overshooting cytokine expression.
2013-05-31 | GSE40281 | GEO
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.
2017-07-01 | E-MTAB-1210 | biostudies-arrayexpress
Project description:The p38 MAP kinases play critical roles in skeletal muscle biology, but the specific processes that they regulate remain poorly defined. Here we find that activity of p38α/β is important not only for early phases of myoblast differentiation, but also in later stages of myocyte fusion and myofibrillogenesis. By treating C2 myoblasts with the pro-myogenic growth factor, IGF-I, we were able to overcome the early block in differentiation imposed by co-incubation with the p38 chemical inhibitor, SB202190. Yet, IGF-I could not overcome the later impairment of muscle cell fusion, as marked by the nearly complete absence of multinucleated myofibers. Removal of SB202190 from the medium of differentiating myoblasts showed that the fusion block was reversible, as multinucleated myofibers were detected several hours later, and reached ~90% of the culture within 30 hours. Analysis by quantitative mass spectroscopy of proteins that changed in abundance following removal of the inhibitor revealed a cohort of up-regulated muscle-enriched molecules that may be important for both myofibrillogenesis and fusion. We have thus developed a model system that allows separation of myoblast differentiation from muscle cell fusion, which should be useful in identifying specific steps regulated by p38 MAP kinase-mediated signaling in myogenesis.
2018-10-24 | PXD002413 | Pride
Project description:Nitric oxide (NO) can stabilize mRNA by activating p38 mitogen-activated protein kinase (MAPK). Here, transcript stabilization by NO was investigated in human THP-1 cells using microarrays. After LPS pre-stimulation, cells were treated with actinomycin D and then exposed to NO without or with the p38 MAPK inhibitor SB202190. The decay of 220 mRNAs was affected; most were stabilized by NO. Unexpectedly, SB202190 often enhanced rather than antagonized transcript stability. NO activated p38 MAPK and Erk1/2; SB202190 blocked p38 MAPK, but further activated Erk1/2. PCR confirmed that NO and SB202190 could additively stabilize mRNA, an effect abolished by Erk1/2 inhibition. In affected genes, these responses were associated with CU-rich elements (CURE) in 3' un-translated regions. NO stabilized the mRNA of a CURE-containing reporter gene, while repressing translation. Dominant-negative Mek1, an Erk1/2 inhibitor, abolished this effect. NO similarly stabilized, but blocked translation of MAP3K7IP2, a natural CURE-containing gene. NO increased hnRNP translocation to the cytoplasm and binding to CURE. Over-expression of hnRNP K, like NO, repressed translation of CURE-containing mRNA. These findings define a sequence-specific mechanism of NO-triggered gene regulation that stabilizes mRNA, but represses translation. Keywords: time course and dose response
2006-07-27 | GSE4228 | GEO
Project description:Nicotinamide, the amide form of vitamin B3, is essential to maintain the human fetal development. It benefits the ectoderm and endoderm development, but its influence in mesoderm differentiation is elusive. In this study, we reported that nicotinamide regulated the gene expression of cardiovascular system, and it induced functional cardiomyocytes which was independent of canonical WNT signaling. Through a kinase screening, we found that nicotinamide inhibited the activity of P38δ to promote cardiomyocyte differentiation. Furthermore, we compared the gene expression of cardiomyocytes induced by WNT inhibitor IWP-2, nicotinamide or P38 inhibitor SB202190. The results showed that the cardiomyocytes induced by nicotinamide had similar gene expression profile compared with P38 inhibitor, which indicated nicotinamide promoted cardiac differentiation via the inhibition of P38.
2021-12-01 | GSE154454 | GEO
Project description:Nicotinamide, the amide form of vitamin B3, is essential to maintain the human fetal development. It benefits the ectoderm and endoderm development, but its influence in mesoderm differentiation is elusive. In this study, we reported that nicotinamide regulated the gene expression of cardiovascular system, and it induced functional cardiomyocytes which was independent of canonical WNT signaling. Through a kinase screening, we found that nicotinamide inhibited the activity of P38δ to promote cardiomyocyte differentiation. Furthermore, we compared the gene expression of cardiomyocytes induced by WNT inhibitor IWP-2, nicotinamide or P38 inhibitor SB202190. The results showed that the cardiomyocytes induced by nicotinamide had similar gene expression profile compared with P38 inhibitor, which indicated nicotinamide promoted cardiac differentiation via the inhibition of P38.
2021-12-01 | GSE154453 | GEO
Project description:Astroglia, the star-shaped cells found throughout the central nervous system are the most numerous cell type in the brain. The astroglial response to injury, generically termed reactive astrogliosis, is classically defined by cellular hypertrophy and process extension, increased glial filament production, and some degree of proliferation. Astrogliosis and its functional outcomes, glial scar formation and neuroinflammation, are often viewed as detrimental to recovery. However, increasing evidence points to neuroprotective roles of reactive astroglia in the setting of brain injury. Therapeutic modulation of this double-edged sword will require detailed knowledge of mechanisms by which specific signals induce detrimental and beneficial phenotypes. This proposal is is a logical extension of a published, peer reviewed study (Heffron DS and Mandell JW, Opposing roles of ERK and p38 MAP kinases in FGF2-induced astroglial process extension. Mol Cell Neurosci 2005, 28:779-90). The downstream gene expression changes underlying these pathway-specific responses are largely unknown. The data generated from the proposed project will delineate pathway-specific gene expression responses of astroglia to fibroblast growth factors. This information will allow a rational approach to pharmacological approaches to modulate reactive astrogliosis in brain and spinal cord injury. Determine the astroglial gene expression program elicited by fibroblast growth factor-2, and dissect specific contributions of the ERK and p38 MAP kinase pathways using highly specific pharmacological inhibitors. FGF2, acting via two distinct intracellular signaling pathways, ERK- and p38 MAPK, leads to pathway-specific gene expression changes in astrocytes which promote the morphological plasticity (ERK-dependent) and pro-inflammatory properties (p38-dependent) of reactive astroglia. Cell culture; Neonatal primary astrocyte cultures are prepared exactly as previously described (Heffron and Mandell, 2005), using slight modifications of established protocols (McCarthy and de Vellis, 1980). Astrocytes prepared with these methods comprised greater than 95% of cell cultures as determined by GFAP staining. Microglia are present as a contaminating cell type at a percentage of 3.6 ± 0.9% as determined by CD11B staining. For process induction experiments, cells are trypsinized and replated in DMEM with 1% fetal bovine serum. This low serum concentration is necessary for good adhesion of the cells. Pharmacological inhibitors are dissolved in DMSO and added 2 h later. P38 MAP kinase inhibitors SB202190 (Calbiochem) and the MEK inhibitor U0126 (Promega) are used at 20 µM. We previously determined that the inactive analog of SB 202190, SB202474 (Calbiochem) had no effects on pathway activation or astrocyte morphology. Therefore, the inactive drug analog will not be used in the array experiments. Final DMSO concentration in the drug treatments and vehicle controls is 0.2%. Human recombinant FGF2 (obtained from the National Cancer Institute Preclinical Repository) is used at 25 ng/ml, based on extensive dose/response analyses in our published work.
2008-06-15 | E-GEOD-6675 | biostudies-arrayexpress
Project description:Tumor Progression Locus 2 (TPL-2) kinase mediates Toll-like Receptor (TLR) activation of ERK1/2 and p38-alpha MAP kinases in myeloid cells to modulate expression of key cytokines in innate immunity. This study identified a novel MAP kinase-independent regulatory function for TPL-2 in phagosome maturation, an essential process for killing of phagocytosed bacteria. TPL-2 catalytic activity was demonstrated to induce phagosome acidification and proteolysis in primary mouse and human macrophages following uptake of latex beads. Mass spectrometry analysis revealed that blocking TPL-2 catalytic activity significantly altered the protein composition of phagosomes, particularly reducing the abundance of V-ATPase proton pump subunits. Furthermore, TPL-2 was shown to stimulate the phosphorylation of DMXL1, a critical regulator of V-ATPases, to induce phagosome acidification. Consistent with these results, TPL-2 catalytic activity was required for phagosome acidification, activation of phagosome acid-sensitive cathepsins and the efficient killing of Staphylococcus aureus following phagocytic uptake by macrophages. These results indicate that TPL-2 controls the innate immune response of macrophages to bacteria via MAP kinase regulation of gene expression and V-ATPase induction of phagosome maturation.
2021-02-11 | PXD020401 | Pride