A Novel LPS-Inducible C-Type Lectin Is a Transcriptional Target of NF-IL6 in Macrophages
Autor: | M, Matsumoto, T, Tanaka, T, Kaisho, H, Sanjo, N G, Copeland, D J, Gilbert, N A, Jenkins, S, Akira |
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Rok vydání: | 1999 |
Předmět: |
Lipopolysaccharides
Male Mice Knockout Transcription Genetic Immunology Chromosome Mapping Membrane Proteins Nuclear Proteins DNA-Binding Proteins Mice Inbred C57BL Mice Gene Expression Regulation Lectins CCAAT-Enhancer-Binding Proteins Macrophages Peritoneal Animals Immunology and Allergy Female Lectins C-Type Cloning Molecular Promoter Regions Genetic Protein Binding Transcription Factors |
Zdroj: | The Journal of Immunology. 163:5039-5048 |
ISSN: | 1550-6606 0022-1767 |
Popis: | C-type lectins serve multiple functions through recognizing carbohydrate chains. Here we report a novel C-type lectin, macrophage-inducible C-type lectin (Mincle), as a downstream target of NF-IL6 in macrophages. NF-IL6 belongs to the CCAAT/enhancer binding protein (C/EBP) of transcription factors and plays a crucial role in activated macrophages. However, what particular genes are regulated by NF-IL6 has been poorly defined in macrophages. Identification of downstream targets is required to elucidate the function of NF-IL6 in more detail. To identify downstream genes of NF-IL6, we screened a subtraction library constructed from wild-type and NF-IL6-deficient peritoneal macrophages and isolated Mincle that exhibits the highest homology to the members of group II C-type lectins. Mincle mRNA expression was strongly induced in response to several inflammatory stimuli, such as LPS, TNF-α, IL-6, and IFN-γ in wild-type macrophages. In contrast, NF-IL6-deficient macrophages displayed a much lower level of Mincle mRNA induction following treatment with these inflammatory reagents. The mouse Mincle proximal promoter region contains an indispensable NF-IL6 binding element, demonstrating that Mincle is a direct target of NF-IL6. The Mincle gene locus was mapped at 0.6 centiMorgans proximal to CD4 on mouse chromosome 6. |
Databáze: | OpenAIRE |
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