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Cell type-specific activation of mitogen-activated protein kinases by CpG-DNA controls interleukin-12 release from antigen-presenting cells.
- Source :
-
The EMBO journal [EMBO J] 1999 Dec 15; Vol. 18 (24), pp. 6973-82. - Publication Year :
- 1999
-
Abstract
- Activation of antigen-presenting cells (APCs) by invariant constituents of pathogens such as lipopolysaccharide (LPS) or bacterial DNA (CpG-DNA) initiates immune responses. We have analyzed the mitogen-activated protein kinase (MAPK) pathways triggered by CpG-DNA and their significance for cytokine production in two subsets of APCs, i.e. macrophages and dendritic cells (DCs). We found that CpG-DNA induced extracellular signal-regulated kinase (ERK) activity in macrophages in a classic MEK-dependent way. This pathway up-regulated tumor necrosis factor production but down-regulated interleukin (IL)-12 production. However, in DCs, which produce large amounts of IL-12, CpG-DNA and LPS failed to induce ERK activity. Consistent with a specific negative regulatory role for ERK in macrophages, chemical activation of this pathway in DCs suppressed CpG-DNA-induced IL-12 production. Overall, these results imply that differential activation of MAP kinase pathways is a basic mechanism by which distinct subsets of innate immune cells regulate their effector functions.
- Subjects :
- Animals
Antigen-Presenting Cells drug effects
Antigen-Presenting Cells immunology
Bone Marrow Cells cytology
Bone Marrow Cells immunology
Cell Line
Cells, Cultured
Dendritic Cells drug effects
Dendritic Cells immunology
Dinucleoside Phosphates
Gene Expression Regulation immunology
Lipopolysaccharides pharmacology
Luciferases genetics
Macrophages drug effects
Macrophages immunology
Mice
Mice, Inbred C57BL
Recombinant Proteins biosynthesis
Thionucleotides
Transfection
Tumor Necrosis Factor-alpha genetics
Antigen-Presenting Cells physiology
Dendritic Cells physiology
Interleukin-12 biosynthesis
Interleukin-12 genetics
Macrophages physiology
Mitogen-Activated Protein Kinases metabolism
Oligodeoxyribonucleotides pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0261-4189
- Volume :
- 18
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- The EMBO journal
- Publication Type :
- Academic Journal
- Accession number :
- 10601019
- Full Text :
- https://doi.org/10.1093/emboj/18.24.6973