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Cell type‐specific activation of mitogen‐activated protein kinases by CpG‐DNA controls interleukin‐12 release from antigen‐presenting cells
Author(s) -
Häcker Hans,
Mischak Harald,
Häcker Georg,
Eser Sema,
Prenzel Norbert,
Ullrich Axel,
Wagner Hermann
Publication year - 1999
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/18.24.6973
Subject(s) - biology , mapk/erk pathway , microbiology and biotechnology , innate immune system , kinase , protein kinase a , immune system , cpg site , signal transduction , immunology , dna methylation , biochemistry , gene expression , gene
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.