Linked Life Data

18093851

Source:http://linkedlifedata.com/resource/pubmed/id/18093851

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-4-18
pubmed:abstractText
This study was designed to evaluate effects of specific p38 MAP kinase inhibition on gene and protein expression of essential hematopoietic cytokines in primary human bone marrow stromal cells (HBMSC) and to identify downstream transcription factors (TF) regulated by the p38 MAP kinase signalling pathway. In vitro effects of p38 inhibitors (p38i) on cytokine regulation were compared to inhibitors of other major signalling pathways including PI3 kinase, JNK, MEK-1, NF-kappaB or protein kinase C (PKC). HBMSC were pre-treated with p38i (SB-203580) for 1 h and then stimulated with 200 ng/ml lipopolysaccharide (LPS). Supernatants and RNA were collected 6 h post LPS treatment for quantitative protein and mRNA analyses by ELISA and real-time RT-PCR, respectively, for interleukin-6 (IL-6), interleukin-11 (IL-11), granulocyte-monocyte colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF) and Activin A. Effects of the inhibitors of PI3 kinase (LY294002), JNK (synthetic inhibitory peptide), MEK-1 (PD90859), NF-kappaB (pyrrolidinedithiocarbamate (PDTC)) and protein kinase C (calphostin C) on HBMSC expression hematopoietic cytokines were evaluated and compared. SB-203580 caused dose-dependent decreases in cytokine protein expression and decreased IL-6 and IL-11 mRNA expression. Of the pathway inhibitors examined, only NF-kappaB elicited similar effects on cytokine protein and mRNA expression. p38-regulated transcription factor activity was assessed using a DNA/Protein array. Several TFs linked to cytokine regulation were modulated by SB-203580, with 10 of 21 p38-regulated TFs identified have not been previously linked to downstream p38 signalling. These observations in cultured HBMSC have illustrated the involvement of cytokine proteins, mRNA and TF activities and may improve the current understanding of the in vivo p38i suppression of erythropoiesis. In addition, these results suggest that IL-6, IL-11, GM-CSF, G-CSF and Activin A are similarly regulated by p38 and NF-kappaB and that the MEK1, JNK and PKC pathways appear to play a more limited role in modulating cytokine expression in HBMSC.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1096-0961
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
40
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
370-80
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18093851-Adult, pubmed-meshheading:18093851-Bone Marrow Cells, pubmed-meshheading:18093851-Cells, Cultured, pubmed-meshheading:18093851-Cytokines, pubmed-meshheading:18093851-Enzyme Inhibitors, pubmed-meshheading:18093851-Hematopoiesis, pubmed-meshheading:18093851-Humans, pubmed-meshheading:18093851-Imidazoles, pubmed-meshheading:18093851-Lipopolysaccharides, pubmed-meshheading:18093851-MAP Kinase Signaling System, pubmed-meshheading:18093851-Male, pubmed-meshheading:18093851-NF-kappa B, pubmed-meshheading:18093851-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:18093851-Protein Array Analysis, pubmed-meshheading:18093851-Pyridines, pubmed-meshheading:18093851-Stromal Cells, pubmed-meshheading:18093851-Transcription Factors, pubmed-meshheading:18093851-p38 Mitogen-Activated Protein Kinases
pubmed:articleTitle
Role of p38 in regulation of hematopoiesis: effect of p38 inhibition on cytokine production and transcription factor activity in human bone marrow stromal cells.
pubmed:affiliation
GlaxoSmithKline, 709 Swedeland Road, Mail Stop UE0364, King of Prussia, PA 19406, USA. Marshall.2.Scicchitano@gsk.com
pubmed:publicationType
Journal Article