Abstract
Results We identified GM-CSF-dependent regulation of 402 genes, including important immune-regulatory molecules. Functional clustering of GM-CSF-regulated genes indicated induction of monocytic properties such as lymphocyte activation and tumour necrosis factor (TNF) receptor binding as well as repression of apoptosis, oxidative burst, cell motility and migration. Expression data show an up-regulation of M2-phenotype genes (CCL 13, 23 and 17) and down-regulation of M1-phenotype genes (CXCL10, 11 and 13) indicating a GM-CSF induced alternative macrophage activation. Independent functional analysis revealed suppression of apoptosis by GM-CSF. However GM-CSF induces apoptosis in monocytes activated by TNFα which may contribute to anti-inflammatory actions of GM-CSF treatment in vivo.
Highlights
Monocytes and macrophages may either promote or down-regulate inflammatory reactions depending on their state of activation
The results were independently confirmed by real-time polymerase chain reaction (PCR), flow cytometry and assessed by independent functional assays evaluating the influence of defined cytokine combinations (+Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF), ± IL-4, ± Il-6, ± IL-8, ± TNFα, ± IFNγ)
GM-CSF treatment did not cause a transitory amplification of innate immunity but results in differentiation of a specific phenotype which may be actively involved in resolution of acute and possibly chronic inflammatory reactions
Summary
Address: 1Department of Paediatrics, University of Muenster, Münster, Germany, 2Institute of Immunology, University of Muenster, Münster, Germany and 3Department of Dermatology, University of Muenster, Münster, Germany. Published: 15 September 2008 Pediatric Rheumatology 2008, 6(Suppl 1):P125 doi:10.1186/1546-0096-6-S1-P125. 15th Paediatric Rheumatology European Society (PreS) Congress Wietse Kuis, Patricia Woo, Angelo Ravelli, Hermann Girschick, Michaël Hofer, Johannes Roth, Rotraud K Saurenmann, Alberto Martini, Pavla Dolezova, Janjaap van der Net, Pierre Quartier, Lucy Wedderburn and Jan Scott Meeting abstracts – A single PDF containing all abstracts in this Supplement is available here.
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