15 kDa Granulysin versus GM-CSF for monocytes differentiation: analogies and differences at the transcriptome level
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RESEARCH
Open Access
15 kDa Granulysin versus GM-CSF for monocytes differentiation: analogies and differences at the transcriptome level Luciano Castiello1, David F Stroncek1*, Michael W Finn2, Ena Wang3, Francesco M Marincola3, Carol Clayberger2, Alan M Krensky2 and Marianna Sabatino1
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.
Background Many immunotherapies are based on the use of immunomodulators for the activation or suppression of the immune response. These immunomodulators include cytokines, chemokines and growth factors that act on specific subsets of immune cells in vivo or ex vivo, alone or in combination, to modulate an immune response. GM-CSF is a growth factor encoded by the CSF2 gene [1]. It is a glycoprotein naturally produced by lymphocytes and monocytes that induces the ex vivo proliferation of hematopoietic progenitor cells to form colonies of mature blood cells[2]. In addition, GM-CSF induces the * Correspondence: [email protected] 1 Cell Processing Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA Full list of author information is available at the end of the article
proliferation of monocytes-macrophages and secretion of inflammatory cytokines such as tumor necrosis factor (TNF) and interleukin 1 (IL-1) [3]. It plays an important role in the activation of dendritic cells (DCs), T cells and natural killer (NK) cells[2
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