15 kDa Granulysin versus GM-CSF for monocytes differentiation

Analogies and differences at the transcriptome level

Luciano Castiello, David F. Stroncek, Michael W. Finn, Ena Wang, Francesco M. Marincola, Carol Clayberger, Alan M. Krensky, Marianna Sabatino

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Granulysin is an antimicrobial and proinflammatory protein with several isoforms. While the 9 kDa isoform is a well described cytolytic molecule with pro-inflammatory activity, the functions of the 15 kDa isoform is less well understood. Recently it was shown that 15 kDa Granulysin can act as an alarmin that is able to activate monocytes and immature dendritic cells. Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) is a growth factor widely used in immunotherapy both for in vivo and ex vivo applications, especially for its proliferative effects.Methods: We analyzed gene expression profiles of monocytes cultured with 15 kDa Granulysin or GM-CSF for 4, 12, 24 and 48 hours to unravel both similarities and differences between the effects of these stimulators.Results: The analysis revealed a common signature induced by both factors at each time point, but over time, a more specific signature for each factor became evident. At all time points, 15 kDa Granulysin induced immune response, chemotaxis and cell adhesion genes. In addition, only 15 kDa Granulsyin induced the activation of pathways related to fundamental dendritic cell functions, such as co-stimulation of T-cell activation and Th1 development. GM-CSF specifically down-regulated genes related to cell cycle arrest and the immune response. More specifically, cytokine production, lymphocyte mediated immunity and humoral immune response were down-regulated at late time points.Conclusion: This study provides important insights on the effects of a novel agent, 15 kDa granulysin, that holds promise for therapeutic applications aimed at the activation of the immune response.

Original languageEnglish
Article number41
JournalJournal of Translational Medicine
Volume9
DOIs
Publication statusPublished - 18 Apr 2011
Externally publishedYes

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Granulocyte-Macrophage Colony-Stimulating Factor
Transcriptome
Monocytes
Protein Isoforms
Chemical activation
Genes
Dendritic Cells
T-cells
Lymphocytes
Cell adhesion
Gene expression
Intercellular Signaling Peptides and Proteins
Chemotaxis
Humoral Immunity
Cell Cycle Checkpoints
Cells
Cell Adhesion
Immunotherapy
Cytokines
Immunity

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

15 kDa Granulysin versus GM-CSF for monocytes differentiation : Analogies and differences at the transcriptome level. / Castiello, Luciano; Stroncek, David F.; Finn, Michael W.; Wang, Ena; Marincola, Francesco M.; Clayberger, Carol; Krensky, Alan M.; Sabatino, Marianna.

In: Journal of Translational Medicine, Vol. 9, 41, 18.04.2011.

Research output: Contribution to journalArticle

Castiello, Luciano ; Stroncek, David F. ; Finn, Michael W. ; Wang, Ena ; Marincola, Francesco M. ; Clayberger, Carol ; Krensky, Alan M. ; Sabatino, Marianna. / 15 kDa Granulysin versus GM-CSF for monocytes differentiation : Analogies and differences at the transcriptome level. In: Journal of Translational Medicine. 2011 ; Vol. 9.
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