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Suppression of NF-κB and IRF-1-induced transcription of the murine IL-12 p40 by transforming growth factor-β Smad pathway in macrophages

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Abstract

In this study, we have characterized the negative regulation of the IL-12 p40 expression by TGF-β in macrophages. Although murine IL-12 p40 promoter contains a putative TGF-β inhibitory element (TIE), neither mutation nor deletion of the TIE had any effect on the inhibitory activity of TGF-β. The NF-κB p65 and interferon regulatory factor (IRF)-1 induced promoter activity was suppressed by the expression of a constitutively active TGF-β type I receptor in the presence of Smad3 and Smad4, which was abrogated by expression of an inhibitory Smad, Smad7. Transcription of a reporter gene containing three copies of both NF-κB and IRF-1 elements from the IL-12 p40 promoter was significantly repressed by activation of Smad-dependent TGF-β pathway. In contrast, reporter containing three copies of either the NF-κB or IRF-1 sites was not affected by TGF-β-Smad pathway. These findings indicated that both the NF-κB and IRF-1 sites are required for the repression of promoter activity of IL-12 p40 by TGF-β.

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Acknowledgments

This work was supported by Grant-in-Aid for Scientific Research (18580300) from Japan Society for the Promotion of Science and a grant for Chemical Biology Research Program from RIKEN (to K.O.).

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Authors and Affiliations

  1. Laboratory of Cellular Biochemistry, RIKEN, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan

    Kenji Ogawa & Masafumi Tsujimoto

  2. Laboratory of Nutrition, Azabu University School of Veterinary Medicine, 1-17-71 Fuchinobe, Sagamihara, Kanagawa, 229-8501, Japan

    Masayuki Funaba

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  1. Kenji Ogawa
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  2. Masayuki Funaba
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  3. Masafumi Tsujimoto
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Correspondence to Kenji Ogawa.

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Ogawa, K., Funaba, M. & Tsujimoto, M. Suppression of NF-κB and IRF-1-induced transcription of the murine IL-12 p40 by transforming growth factor-β Smad pathway in macrophages. Mol Cell Biochem 308, 9–15 (2008). https://doi.org/10.1007/s11010-007-9605-4

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  • DOI: https://doi.org/10.1007/s11010-007-9605-4

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