Gene expression profiling of macrophages: implications for an immunosuppressive effect of dissolucytotic gold ions

2.50
Hdl Handle:
http://hdl.handle.net/10033/620771
Title:
Gene expression profiling of macrophages: implications for an immunosuppressive effect of dissolucytotic gold ions
Authors:
Seifert, Oliver; Matussek, Andreas; Sjögren, Florence; Geffers, Robert; Anderson, Chris D
Abstract:
Abstract Background Gold salts has previously been used in the treatment of rheumatoid arthritis but have been replaced by biologicals such as TNF-α inhibitors. The mechanisms behind the anti-inflammatory effect of metallic gold ions are still unknown, however, recent data showed that charged gold atoms are released from pure metallic gold implants by macrophages via a dissolucytosis membrane, and that gold ions are taken up by local macrophages, mast cells and to some extent fibroblasts. These findings open the question of possible immunomodulatory effects of metallic gold and motivate efforts on a deeper understanding of the effect of metallic gold on key inflammatory cells as macrophages. Methods Human macrophage cells (cell line THP-1) were grown on gold foils and intracellular uptake was analysed by autometallography. The impact of phagocytised gold ions on viability of THP-1 cells was investigated by trypan blue staining and TUNEL assay. The global gene expression profile of THP-1 cells after incorporation of gold ions was studied using microarray analysis comprising approximately 20,000 genes. The gene expression data was confirmed by measurement of secreted proteins. Results Autometallography showed intracellular uptake of gold ions into THP-1 cells. No significant effect on viability of THP-1 cells was demonstrated. Our data revealed a unique gene expression signature of dissolucytotic THP-1 cells that had taken up gold ions. A large number of regulated genes were functionally related to immunomodulation. Gold ion uptake induced downregulation of genes involved in rheumatoid arthritis such as hepatocyte growth factor, tenascin-C, inhibitor of DNA binding 1 and 3 and matrix metalloproteinase 13. Conclusion The data obtained in this study offer new insights into the mode of action of gold ions and suggest for the investigation of effects on other key cells and a possible future role of metallic gold as implants in rheumatoid arthritis or other inflammatory conditions.
Citation:
Journal of Inflammation. 2012 Nov 09;9(1):43
Issue Date:
9-Nov-2012
URI:
http://dx.doi.org/10.1186/1476-9255-9-43; http://hdl.handle.net/10033/620771
Type:
Journal Article
Appears in Collections:
publications of the research group genomeanalytics (GMAK)

Full metadata record

DC FieldValue Language
dc.contributor.authorSeifert, Oliveren
dc.contributor.authorMatussek, Andreasen
dc.contributor.authorSjögren, Florenceen
dc.contributor.authorGeffers, Roberten
dc.contributor.authorAnderson, Chris Den
dc.date.accessioned2017-01-27T10:19:06Z-
dc.date.available2017-01-27T10:19:06Z-
dc.date.issued2012-11-09en
dc.identifier.citationJournal of Inflammation. 2012 Nov 09;9(1):43en
dc.identifier.urihttp://dx.doi.org/10.1186/1476-9255-9-43en
dc.identifier.urihttp://hdl.handle.net/10033/620771-
dc.description.abstractAbstract Background Gold salts has previously been used in the treatment of rheumatoid arthritis but have been replaced by biologicals such as TNF-α inhibitors. The mechanisms behind the anti-inflammatory effect of metallic gold ions are still unknown, however, recent data showed that charged gold atoms are released from pure metallic gold implants by macrophages via a dissolucytosis membrane, and that gold ions are taken up by local macrophages, mast cells and to some extent fibroblasts. These findings open the question of possible immunomodulatory effects of metallic gold and motivate efforts on a deeper understanding of the effect of metallic gold on key inflammatory cells as macrophages. Methods Human macrophage cells (cell line THP-1) were grown on gold foils and intracellular uptake was analysed by autometallography. The impact of phagocytised gold ions on viability of THP-1 cells was investigated by trypan blue staining and TUNEL assay. The global gene expression profile of THP-1 cells after incorporation of gold ions was studied using microarray analysis comprising approximately 20,000 genes. The gene expression data was confirmed by measurement of secreted proteins. Results Autometallography showed intracellular uptake of gold ions into THP-1 cells. No significant effect on viability of THP-1 cells was demonstrated. Our data revealed a unique gene expression signature of dissolucytotic THP-1 cells that had taken up gold ions. A large number of regulated genes were functionally related to immunomodulation. Gold ion uptake induced downregulation of genes involved in rheumatoid arthritis such as hepatocyte growth factor, tenascin-C, inhibitor of DNA binding 1 and 3 and matrix metalloproteinase 13. Conclusion The data obtained in this study offer new insights into the mode of action of gold ions and suggest for the investigation of effects on other key cells and a possible future role of metallic gold as implants in rheumatoid arthritis or other inflammatory conditions.en
dc.titleGene expression profiling of macrophages: implications for an immunosuppressive effect of dissolucytotic gold ionsen
dc.typeJournal Articleen
dc.language.rfc3066enen
dc.rights.holderSeifert et al.; licensee BioMed Central Ltd.en
dc.date.updated2015-09-04T08:27:20Zen
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