Klf10 inhibits IL-12p40 production in macrophage colony-stimulating factor-induced mouse bone marrow-derived macrophages

Wei Zhang, Xuelian Wang, Xiaoping Xia, Xia Liu, Shanshan Suo, Jing Guo, Min Li, Wenqiang Cao, Zhijian Cai, Zhaoyuan Hui, Malayannan Subramaniam, Thomas C. Spelsberg, Jianli Wang, Lie Wang

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Bone marrow-derived macrophages (BMMs) treated with granulocyte-macrophage colony-stimulating factor (GM-CSF) or macrophage colony-stimulating factor (M-CSF), differentiate into GM-CSF-induced mouse bone marrow-derived macrophages (GM-BMMs) or M-CSF-induced mouse bone marrow-derived macrophages (M-BMMs), which have an M1 or M2 profile, respectively. GM-BMMs produce large amounts of proinflammatory cytokines and mediate resistance to pathogens, whereas M-BMMs produce antiinflammatory cytokines that contribute to tissue repair and remodeling. M-BMMs stimulated with lipopolysaccharide (LPS) are in an antiinflammatory state, with an IL-12lowIL-10high phenotype. However, the regulation of this process remains unclear. Klf10 belongs to the family of Krüppel-like transcription factors and was initially described as a TGF-β inducible early gene 1. IL-12p40 is upregulated in LPS-stimulated M-BMMs from Klf10-deficient mice, but downregulated during Klf10 overexpression. Klf11, another member of the Krüppel-like factor family, can also repress the production of IL-12p40. Furthermore, Klf10 binds to the CACCC element of the IL-12p40 promoter and inhibits its transcription. We have therefore identified Klf10 as a transcription factor that regulates the expression of IL-12p40 in M-BMMs.

Original languageEnglish (US)
Pages (from-to)258-269
Number of pages12
JournalEuropean Journal of Immunology
Volume43
Issue number1
DOIs
StatePublished - Jan 2013

Keywords

  • IL-12p40
  • Inflammatory factor
  • Klf10
  • Macrophage
  • Transcription factor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Zhang, W., Wang, X., Xia, X., Liu, X., Suo, S., Guo, J., Li, M., Cao, W., Cai, Z., Hui, Z., Subramaniam, M., Spelsberg, T. C., Wang, J., & Wang, L. (2013). Klf10 inhibits IL-12p40 production in macrophage colony-stimulating factor-induced mouse bone marrow-derived macrophages. European Journal of Immunology, 43(1), 258-269. https://doi.org/10.1002/eji.201242697