scholarly journals Differential Gene Expression Profile of Human Neutrophils Cultured withPlasmodium falciparum-Parasitized Erythrocytes

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Mohamad Alaa Terkawi ◽  
Ryo Takano ◽  
Kentaro Kato
Keyword(s):  
Gene Expression ◽  
Inflammatory Diseases ◽  
Transcriptional Response ◽  
Enrichment Analysis ◽  
Mitogen Activated Protein Kinase ◽  
Therapeutic Interventions ◽  
Human Neutrophils ◽  
Surface Receptors ◽  
Genes Encoding ◽  
Mitogen Activated Protein

Neutrophils (PMNs) are the most abundant cellular component of our innate immune system, where they play central roles in the pathogenesis of and resistance to a broad range of diseases. However, their roles in malarial infection remain poorly understood. Therefore, we examined the transcriptional gene profile of human PMNs in response toPlasmodium falciparum-parasitized erythrocytes (iRBCs) by using oligonucleotide microarrays. Results revealed that PMNs induced a broad and vigorous set of changes in gene expression in response to malarial parasites, represented by 118 upregulated and 216 downregulated genes. The transcriptional response was characterized by the upregulation of numerous genes encoding multiple surface receptors, proteins involved in signal transduction pathways, and defense response proteins. This response included a number of genes which are known to be involved in the pathogenesis of malaria and other inflammatory diseases. Gene enrichment analysis suggested that the biological pathways involved in the PMN responses to the iRBCs included insulin receptor, Jak-STAT signaling pathway, mitogen-activated protein kinase (MAPK), and interleukin and interferon-gamma (IFN-γ) signaling pathways. The current study provides fundamental knowledge on the molecular responses of neutrophils to malarial parasites, which may aid in the discovery of novel therapeutic interventions.

scholarly journals Peripheral Injection of SB203580 Inhibits the Inflammatory-Dependent Synthesis of Proinflammatory Cytokines in the Hypothalamus

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Andrzej P. Herman ◽  
Agata Krawczyńska ◽  
Joanna Bochenek ◽  
Hanna Antushevich ◽  
Anna Herman ◽  
...  
Keyword(s):  
Gene Expression ◽  
P38 Mapk ◽  
Proinflammatory Cytokines ◽  
Inflammatory Diseases ◽  
Competitive Inhibitor ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
P38 Mapk Inhibitors ◽  
Mapk Inhibitors ◽  
P38 Mapk Inhibitor

The study was designed to determine the effects of peripheral injection of SB203580 on the synthesis of interleukin- (IL-) 1β, IL-6, and tumor necrosis factor (TNF)αin the hypothalamus of ewes during prolonged inflammation. Inflammation was induced by the administration of lipopolysaccharide (LPS) (400 ng/kg) over 7 days. SB203580 is a selective ATP-competitive inhibitor of the p38 mitogen-activated protein kinase (MAPK), which is involved in the regulation of proinflammatory cytokines IL-1β, IL-6 and TNFαsynthesis. Intravenous injection of SB203580 successfully inhibited (P<0.01) synthesis of IL-1βand reduced (P<0.01) the production of IL-6 in the hypothalamus. The p38 MAPK inhibitor decreased (P<0.01) gene expression of TNFαbut its effect was not observed at the level of TNFαprotein synthesis. SB203580 also reduced (P<0.01) LPS-stimulated IL-1 receptor type 1 gene expression. The conclusion that inhibition of p38 MAPK blocks LPS-induced proinflammatory cytokine synthesis seems to initiate new perspectives in the treatment of chronic inflammatory diseases also within the central nervous system. However, potential proinflammatory effects of SB203580 treatment suggest that all therapies using p38 MAPK inhibitors should be introduced very carefully with analysis of all expected and unexpected consequences of treatment.

scholarly journals Changes in Methylation across Structural and MicroRNA Genes Relevant for Progression and Metastasis in Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5951
Author(s):  
Nitin Patil ◽  
Mohammed L. Abba ◽  
Chan Zhou ◽  
Shujian Chang ◽  
Timo Gaiser ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Cpg Islands ◽  
Enrichment Analysis ◽  
Mitogen Activated Protein Kinase ◽  
Pathway Enrichment Analysis ◽  
Protein Coding ◽  
Normal Tissues ◽  
Mitogen Activated Protein ◽  
Microrna Genes

MiRs are important players in cancer and primarily genetic/transcriptional means of regulating their gene expression are known. However, epigenetic changes modify gene expression significantly. Here, we evaluated genome-wide methylation changes focusing on miR genes from primary CRC and corresponding normal tissues. Differentially methylated CpGs spanning CpG islands, open seas, and north and south shore regions were evaluated, with the largest number of changes observed within open seas and islands. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed several of these miRs to act in important cancer-related pathways, including phosphatidylinositol 3-kinase (PI3K)–protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) pathways. We found 18 miR genes to be significantly differentially methylated, with MIR124-2, MIR124-3, MIR129-2, MIR137, MIR34B, MIR34C, MIR548G, MIR762, and MIR9-3 hypermethylated and MIR1204, MIR17, MIR17HG, MIR18A, MIR19A, MIR19B1, MIR20A, MIR548F5, and MIR548I4 hypomethylated in CRC tumor compared with normal tissue, most of these miRs having been shown to regulate steps of metastasis. Generally, methylation changes were distributed evenly across all chromosomes with predominance for chromosomes 1/2 and protein-coding genes. Interestingly, chromosomes abundantly affected by methylation changes globally were rarely affected by methylation changes within miR genes. Our findings support additional mechanisms of methylation changes affecting (miR) genes that orchestrate CRC progression and metastasis.

scholarly journals The Transcriptional Response to Raf Activation Is Almost Completely Dependent on Mitogen-activated Protein Kinase Kinase Activity and Shows a Major Autocrine Component

2004 ◽  
Vol 15 (7) ◽  
pp. 3450-3463 ◽  
Author(s):  
Almut Schulze ◽  
Barbara Nicke ◽  
Patricia H. Warne ◽  
Simon Tomlinson ◽  
Julian Downward
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Protein Kinase ◽  
Signaling Pathways ◽  
Egf Receptor ◽  
Transcriptional Response ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Epidermal Growth ◽  
Protein Kinase Kinase

The Raf protein kinases are major effectors of Ras GTPases and key components of the transcriptional response to serum factors, acting at least in part through the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway. It has recently been suggested that Raf also may trigger other as yet uncharacterized signaling pathways. Here, we have used cDNA microarrays to dissect changes in gene expression induced by activation of inducible c-Raf-1 constructs in human mammary epithelial and ovarian epithelial cells. The majority of Raf-induced transcriptional responses are shown to be blocked by pharmacological inhibition of the Raf substrate mitogen-activated protein kinase kinase, indicating that potential mitogen-activated protein kinase kinase-independent Raf signaling pathways have no significant influence on gene expression. In addition, we used epidermal growth factor receptor inhibitory drugs to address the contribution of autocrine signaling by Raf-induced EGF family proteins to the Raf transcriptional response. At least one-half of the transcription induced by Raf activation requires epidermal growth factor (EGF) receptor function The EGF receptor-independent component of the Raf transcriptional response is entirely up-regulation of gene expression, whereas the EGF receptor-dependent component is an equal mixture of up- and down-regulation. The use of transcriptional profiling in this way allows detailed analysis of the architecture of signaling pathways to be undertaken.

scholarly journals Peroxide Sensors for the Fission Yeast Stress-activated Mitogen-activated Protein Kinase Pathway

2001 ◽  
Vol 12 (2) ◽  
pp. 407-419 ◽  
Author(s):  
Vicky Buck ◽  
Janet Quinn ◽  
Teresa Soto Pino ◽  
Humberto Martin ◽  
Jose Saldanha ◽  
...  
Keyword(s):  
Gene Expression ◽  
Map Kinase ◽  
Fission Yeast ◽  
Response Regulator ◽  
Transcriptional Response ◽  
Mitogen Activated Protein Kinase ◽  
Regulator Protein ◽  
Protein Map ◽  
Mitogen Activated Protein ◽  
Response Regulator Protein

The Schizosaccharomyces pombe stress-activated Sty1p/Spc1p mitogen-activated protein (MAP) kinase regulates gene expression through the Atf1p and Pap1p transcription factors, homologs of human ATF2 and c-Jun, respectively. Mcs4p, a response regulator protein, acts upstream of Sty1p by binding the Wak1p/Wis4p MAP kinase kinase kinase. We show that phosphorylation of Mcs4p on a conserved aspartic acid residue is required for activation of Sty1p only in response to peroxide stress. Mcs4p acts in a conserved phospho-relay system initiated by two PAS/PAC domain-containing histidine kinases, Mak2p and Mak3p. In the absence of Mak2p or Mak3p, Sty1p fails to phosphorylate the Atf1p transcription factor or induce Atf1p-dependent gene expression. As a consequence, cells lacking Mak2p and Mak3p are sensitive to peroxide attack in the absence of Prr1p, a distinct response regulator protein that functions in association with Pap1p. The Mak1p histidine kinase, which also contains PAS/PAC repeats, does not regulate Sty1p or Atf1p but is partially required for Pap1p- and Prr1p-dependent transcription. We conclude that the transcriptional response to free radical attack is initiated by at least two distinct phospho-relay pathways in fission yeast.

scholarly journals Identification of the functional components of the Ras signaling pathway regulating pituitary cell-specific gene expression.

1994 ◽  
Vol 14 (3) ◽  
pp. 1553-1565 ◽  
Author(s):  
K E Conrad ◽  
J M Oberwetter ◽  
R Vaillancourt ◽  
G L Johnson ◽  
A Gutierrez-Hartmann
Keyword(s):  
Gene Expression ◽  
Pituitary Cell ◽  
Mitogen Activated Protein Kinase ◽  
Specific Gene ◽  
Ras Signaling ◽  
Raf Kinase ◽  
Prolactin Gene ◽  
Ras Signaling Pathway ◽  
Mitogen Activated Protein ◽  
Prolactin Promoter

Ras, a small GTP-binding protein, is required for functional receptor tyrosine kinase signaling. Ultimately, Ras alters the activity of specific nuclear transcription factors and regulates novel patterns of gene expression. Using a rat prolactin promoter construct in transient transfection experiments, we show that both oncogenic Ras and activated forms of Raf-1 kinase selectively stimulated the cellular rat prolactin promoter in GH4 rat pituitary cells. We also show that the Ras signal is completely blocked by an expression vector encoding a dominant-negative Raf kinase. Additionally, using a molecular genetic approach, we determined that inhibitory forms of p42 mitogen-activated protein kinase and an Ets-2 transcription factor interfere with both the Ras and the Raf activation of the rat prolactin promoter. These findings define a functional requirement for these signaling constituents in the activation of the prolactin gene, a cell-specific gene which marks the lactotroph pituitary cell type. Further, this analysis allowed us to order the components in the Ras signaling pathway as it impinges on regulation of prolactin gene transcription as Ras-->Raf kinase-->mitogen-activated protein kinase-->Ets. In contrast, we show that intact c-Jun expression inhibited the Ras-induced activation of the prolactin promoter, defining it as a negative regulator of this pathway, whereas c-Jun was able to enhance the Ras activation of an AP-1-driven promoter in GH4 cells. These data show that c-Jun is not the nuclear mediator of the Ras signal for the highly specialized, pituitary cell-specific prolactin cellular promoter. Thus, we have defined a model system which provides an ideal paradigm for studying Ras/Raf signaling pathways and their effects on neuroendocrine cell-specific gene regulation.

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