Human Gene Set: GSE15139_GMCSF_TREATED_VS_UNTREATED_NEUTROPHILS_UP

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Standard name GSE15139_GMCSF_TREATED_VS_UNTREATED_NEUTROPHILS_UP
Systematic name M7100
Brief description Genes up-regulated in neutrophils treated with CSF2 [GeneID=1437] versus control.
Full description or abstract The objective of this study was to compare the transcriptional repertoire of mature human neutrophils before and after GM-CSF treatment by using oligonucleotide microarrays. Leukotriene B4 (LTB4) is an important pro-inflammatory lipid mediator generated by neutrophils upon activation. Granulocyte/macrophage colony-stimulating factor (GM-CSF) stimulation is known to enhance agonist-mediated LTB4 production of neutrophils within minutes, a process called ?priming?. Here, we demonstrate that GM-CSF also limits the production of LTB4 by neutrophils via a transcriptional mechanism at later time points. We identified hematopoietic specific Ras homologous (RhoH)/translocation three four (TTF), which was induced following GM-CSF stimulation in neutrophils, as a key regulator in this process. Neutrophils derived from RhoH/TTF-deficient (Rhoh-/-) mice demonstrated increased LTB4 production upon activation compared with normal mouse neutrophils. Moreover, neutrophils from cystic fibrosis patients expressed enhanced levels of RhoH/TTF and generated less LTB4 upon activation compared with normal human neutrophils. Taken together, these data suggest that RhoH/TTF represents an inducible feedback inhibitor in neutrophils that is involved in the limitation of innate immune responses.
Collection C7: Immunologic Signature
      IMMUNESIGDB: ImmuneSigDB
Source publication Pubmed 19414807   Authors: Daryadel A,Yousefi S,Troi D,Schmid I,Schmidt-Mende J,Mordasini C,Dahinden CA,Ziemiecki A,Simon HU
Exact source GSE15139_2742_200_UP
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(show 2 gene sets from the same authors)
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Organism Homo sapiens
Contributed by Jernej Godec (Dana-Farber Cancer Institute)
Source platform HUMAN_GENE_SYMBOL
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Version history 7.3: Moved to ImmuneSigDB sub-collection.

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