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 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 kappaB (NF-kappaB) was associated with this IL-10-induced MCP-1 expression. Furthermore, IL-10 suppressed lipopolysaccharide (LPS)-induced NF-kappaB 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-kappaB binding is crucial for down-regulation of MCP-1 by IL-10 in stimulated monocytes/macrophages.
Ikeda
Takashi
T
Third Department of Internal Medicine, National Defense Medical College, Saitama, Japan.
Sato
Ken
K
Kuwada
Naruo
N
Matsumura
Takuya
T
Yamashita
Takuya
T
Kimura
Fumihiko
F
Hatake
Kiyohiko
K
Ikeda
Kazuma
K
Motoyoshi
Kazuo
K
D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000187:drug effects; D025461:Feedback, Physiological; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D016328:NF-kappa B / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D016329:Sp1 Transcription Factor / Q000187:drug effects; D015534:Trans-Activators / Q000187:drug effects
D018932:Chemokine CCL2; D004268:DNA-Binding Proteins; D018793:Interleukin-13; D016328:NF-kappa B; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D016329:Sp1 Transcription Factor; D015534:Trans-Activators; D016753:Interleukin-10; D015847:Interleukin-4