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(Journal of Leukocyte Biology. 2002;72:1198-1205.)
© 2002 by Society for Leukocyte Biology

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

Takashi Ikeda^*, Ken Sato^*, Naruo Kuwada^*, Takuya Matsumura^*, Takuya Yamashita^*, Fumihiko Kimura^*, Kiyohiko Hatake, Kazuma Ikeda and Kazuo Motoyoshi^*

^* Third Department of Internal Medicine, National Defense Medical College, Saitama, Japan;
Division of Clinical Chemotherapy, Japanese Foundation for Cancer Research, Tokyo, Japan; and
Division of Blood Transfusion, Okayama University Medical School, Japan

Correspondence: Kazuo Motoyoshi, M.D., Ph.D., Third Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan. E-mail: motoyosi{at}me.ndmc.ac.jp

Interleukin (IL)-4, IL-10, and IL-13 affect monocyte/macrophage functions including regulation of cytokine production. We analyzed the regulatory effects of these cytokines on cytokine 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-transcriptional 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. Furthermore, 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 important for IL-10-induced MCP-1 expression in resting 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.

Key Words: monocytes • transcription factors • Sp-1 • STAT

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