Dicyanogold effects on lymphokine production.
Having identified dicyanogold(I) as a common metabolite of gold-based antiarthritis drugs, we are investigating the effects of the compound on the production of lymphokines. Handel, et al. 1 suggested that the transcription factor AP-1, critical to the production of a number of cytokines, might be the target for gold compounds because of a critical cysteine within its DNA binding region. Using Jurkat cells, an established cell line as a model for CD4(+) lymphocytes, we have shown that dicyanogold inhibits the binding of AP-1 to DNA and inhibits the synthesis of IL-2 mRNA and protein. In a macrophage line, THP-1, which synthesizes IL-1beta in response to mitogen, we have shown that dicyanogold inhibits the binding of a second transcription factor, CREB to DNA. Incubation of THP-1 cells with dicyanogold inhibits the production of IL-1beta mRNA. These results suggest that the mechanism of action of gold drugs may be through their interaction with transcription factors necessary for the immune activation seen in Rheumatoid Arthritis.
Tepperman
K
K
Departments of Biological Sciences and Chemistry and the Biomedical Chemistry Research Center University of Cincinnati Cincinnati OH 45221-0006 USA.
Roy
P W
PW
Moloney
B F
BF
Elder
R C
RC