Klf10 inhibits IL-12p40 production in macrophage colony-stimulating factor-induced mouse bone marrow-derived macrophages.
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-12(low) IL-10(high)  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.
Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.
Wei
W
Zhang
Xuelian
X
Wang
Xiaoping
X
Xia
Xia
X
Liu
Shanshan
S
Suo
Jing
J
Guo
Min
M
Li
Wenqiang
W
Cao
Zhijian
Z
Cai
Zhaoyuan
Z
Hui
Malayannan
M
Subramaniam
Thomas C
TC
Spelsberg
Jianli
J
Wang
Lie
L
Wang
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D051765:Early Growth Response Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D018836:Inflammation Mediators / Q000378:metabolism; D053762:Interleukin-12 Subunit p40 / Q000235:genetics / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016173:Macrophage Colony-Stimulating Factor / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic / Q000235:genetics; D014158:Transcription, Genetic / Q000276:immunology; D019076:Transgenes / Q000235:genetics
D016207:Cytokines; D051765:Early Growth Response Transcription Factors; D018836:Inflammation Mediators; D053762:Interleukin-12 Subunit p40; C569958:KLF10 protein, mouse; D051741:Kruppel-Like Transcription Factors; D016173:Macrophage Colony-Stimulating Factor