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

10 Citations (Scopus)

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

Fingerprint

Interleukin-12 Subunit p40
Macrophage Colony-Stimulating Factor
Macrophages
Granulocyte-Macrophage Colony-Stimulating Factor
Lipopolysaccharides
Anti-Inflammatory Agents
Transcription Factors
Cytokines
Down-Regulation
Phenotype

Keywords

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

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Klf10 inhibits IL-12p40 production in macrophage colony-stimulating factor-induced mouse bone marrow-derived macrophages. / Zhang, Wei; Wang, Xuelian; Xia, Xiaoping; Liu, Xia; Suo, Shanshan; Guo, Jing; Li, Min; Cao, Wenqiang; Cai, Zhijian; Hui, Zhaoyuan; Subramaniam, Malayannan; Spelsberg, Thomas C.; Wang, Jianli; Wang, Lie.

In: European Journal of Immunology, Vol. 43, No. 1, 01.2013, p. 258-269.

Research output: Contribution to journalArticle

Zhang, W, Wang, X, Xia, X, Liu, X, Suo, S, Guo, J, Li, M, Cao, W, Cai, Z, Hui, Z, Subramaniam, M, Spelsberg, TC, 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, vol. 43, no. 1, pp. 258-269. https://doi.org/10.1002/eji.201242697
Zhang, Wei ; Wang, Xuelian ; Xia, Xiaoping ; Liu, Xia ; Suo, Shanshan ; Guo, Jing ; Li, Min ; Cao, Wenqiang ; Cai, Zhijian ; Hui, Zhaoyuan ; Subramaniam, Malayannan ; Spelsberg, Thomas C. ; Wang, Jianli ; Wang, Lie. / Klf10 inhibits IL-12p40 production in macrophage colony-stimulating factor-induced mouse bone marrow-derived macrophages. In: European Journal of Immunology. 2013 ; Vol. 43, No. 1. pp. 258-269.
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AU - Xia, Xiaoping

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AU - Suo, Shanshan

AU - Guo, Jing

AU - Li, Min

AU - Cao, Wenqiang

AU - Cai, Zhijian

AU - Hui, Zhaoyuan

AU - Subramaniam, Malayannan

AU - Spelsberg, Thomas C.

AU - Wang, Jianli

AU - Wang, Lie

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AB - 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.

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