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

Abstract

BackgroundGold salts has previously been used in the treatment of rheumatoid arthritis but have been replaced by biologicals such as TNF-α inhibitors.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.MethodsHuman 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.ResultsAutometallography 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.ConclusionThe 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.

Gold micro‐particles for knee osteoarthritis

“…Increased CDC42 is associated with cartilage degeneration and bone deterioration in a mouse osteoarthritic model (Hu et al, 2018 ). A recent review discusses CDC42 and related biomarkers that govern chondrocytes dedifferentiation and explains how the induced actin crosslinking and polymerization induces loss of cartilage (Seifert et al, 2012 ). IL6 production and chondrocyte inflammation is mediated by CDC42 (Lauer et al, 2021 ).…”

“…We are not aware of any other human studies of intra‐articular micro gold treatment and despite several laboratory studies (Danscher, 2002 ; Danscher & Larsen, 2010 ; Larsen et al, 2008 ; Lauer et al, 2021 ; Seifert et al, 2012 ) and animal studies (Danscher, 2002 ; Havarinasab et al, 2007 ; Hazer et al, 2011 ; Jæger et al, 2007 , 2012 ; Lie et al, 2011 ; Märki et al, 2018 ), only one study involve gold microparticles injected horse carpal joints (Märki et al, 2018 ). There are several studies on the benefits of intravenous treatment of rheumatoid arthritis with goldthiocompounds like Myocrisine © (Clark et al, 2010 ; Lehman et al, 2005 ; Rau, 2005 ).…”

Macrophage: A Potential Target on Cartilage Regeneration

“…These changes could provide a protective environment in the joints of OA patients (25). The use of gold nanoparticles were shown to present anti-inflammatory macrophage response (48), and a pilot study was opened as clinical trial (NCT03389906) in order to see impact of these particles in macrophages from OA knees, though no further analysis concerning M1 and M2 was mentioned.…”

SERS of the anti‐inflammatory drug piroxicam adsorbed on the surface of silver or gold colloids as nanocarrier model

“…Nanomedicine has revealed as a potent tool to carry out drugs until the diseased cells, being noble metals, such as silver and gold, biocompatible, and capable of forming nanoparticles (NPs) suitable to act as drug nanocarriers, although relative toxicity of the drug‐NP systems must be taken into account . Besides this, gold and silver noble metal are known to have also anti‐inflammatory effect and have been used for many years in the therapy of arthritis, silver having antimicrobial properties as added value . Although their mechanism of action is different from that of PX, it is clear that the efficacy of all of them in the treatment of the aforementioned diseases depend on their concentration within the joints, in the synovial fluid .…”