Gold Sodium Thiomalate and Chloroquine Inhibit Cytokine Production in Monocytic THP-1 Cells Through Distinct Transcriptional and Posttranslational Mechanisms.

摘要

Gold sodium thiomalate (GST), chloroquine (CQ), and metho- trexate have been widely used in the therapy of rheumatoid arthritis and other inflammatory conditions. Using the human monocytic cell line THP-1 we have analyzed effects of these drugs on cytokine production and intracellular signaling. GST and CQ were equally effective in reducing lipopolysaccharide (LPS)-induced IL-1beta release while CQ was a more effective inhibitor of TNF-alpha production than GST. Methotrexate did not affect production of these cytokines. CQ reduced IL-1beta mRNA expression and strongly inhibited phosphorylation of mitogen-activated protein kinase (MAPK) p38, and to a lesser extent c-Jun N-terminal kinase and extracellular signal-regulated kinase 1/2. In contrast, GST did not affect cytokine mRNA expression or MAPK activation. However, GST selectively inhibited the activity of the interleukin-1 converting enzyme (ICE)/caspase-1. These data demonstrate that CQ inhibits IL-1beta release from monocytes by interfering with pretranscriptional signaling and TNF-alpha release by posttranslational events whereas GST downregulates IL-1beta secretion by interfering with posttranslational IL-1beta processing.