ab2005

Gold sodium thiomalate suppresses the differentiation and function of human dendritic cells from peripheral blood monocytes

Z.-Y. Wang, A. Morinobu, S. Kawano, J. Saegusa, B. Wang, S. Kumagai

Department of Clinical Pathology and Immunology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.

ABSTRACT
Objective
Gold sodium thiomalate (GST) is a drug commonly used for the treatment of rheumatoid arthritis (RA).
To clarify the mechanism of therapeutic effects of GST on RA, we investigated if GST affects the differentiation of dendritic cells (DC), which are thought to play a pivotal role in RA pathogenesis.

Methods
We generated immature DC (iDC) in vitro from PB monocytes during the 5 to 7-day culture in the presence of IL-4 and GM-CSF. Mature DC (mDC) were induced by adding TNFa on day 5 of the 7-day culture with GM-CSF and IL-4. DC capacity of stimulating T cells was examined in allogenic MLR using generated DC as stimulators. IL-12 production from DC was assayed with ELISA.

Results
We found that: 1) mDC generated in the presence of GST showed lower expression of CD1a, CD83, CD80, CD86, HLA-ABC and HLA-DR compared to control mDC on FACS analysis. 2) GST-treated mDC showed reduced capacity of stimulating allogenic T cells in mixed leukocyte reaction. 3) IL-12p70 production after stimulation with SAC or LPS plus IFNg was markedly reduced in GST-treated mDC.

Conclusion
GST suppresses the differentiation and function of DC generated from peripheral blood monocytes. This previously unknown action may explain the in vivo effects of GST in the treatment of RA.

Key words
Co-stimulatory molecules, dendritic cells, gold sodium thiomalate, interleukin-12, rheumatoid arthritis.

This work is in part supported by a Grant-in-Aid for Scientific Research (C) (11670446) from Japan Society for the Promotion of Science.
Please address reprint requests and correspondence to: Shunichi Kumagai, MD, PhD, Professor, Department of Clinical Pathology and Immunology, Kobe University Graduate School of Medicine, Kusunoki-Cho 7-5-2, Chuo-Ku, Kobe, Hyogo 650-0017, Japan.
E-mail: kumagais@kobe-u.ac.jp