Interleukin-10 differently regulates monocyte chemoattractant protein-1 gene expression depending on the environment in a human monoblastic cell line, UG3

Interleukin (IL)-4, IL-10, and IL-13 af- fect monocyte/macrophage functions including regulation of cytokine production. We analyzed the regulatory effects of these cytokines on cyto- kine production using a human monoblastic cell line, UG3. It is interesting that IL-10 up-regulated, whereas IL-4 and IL-13 down-regulated monocyte chemoattractant protein-1 (MCP-1) production by unstimulated UG3 cells. IL-10-induced expression of MCP-1 mRNA occurred without de novo protein synthesis at transcriptional and post-transcrip- tional levels. The enhancement of binding activity of nuclear factor Sp1 (Sp-1) and signal transducer and activators of transcription (STAT)1 and 3 but not nuclear factor B( NF-B) was associated with this IL-10-induced MCP-1 expression. Further- more, IL-10 suppressed lipopolysaccharide (LPS)- induced NF-B binding but not Sp-1. The present results suggest IL-10 has two contrasting actions on the MCP-1 production of monocytes/macrophages, between the resting and activated conditions. The combination of activated Sp-1 and STATs is impor- tant for IL-10-induced MCP-1 expression in rest- ing monocytes/macrophages, and the inhibition of LPS-induced NF-B binding is crucial for down- regulation of MCP-1 by IL-10 in stimulated monocytes/macrophages. J. Leukoc. Biol. 72: 1198-1205; 2002.