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.
Keywords
BiologyMAPK/ERK pathwayCell biologyInnate immune systemKinaseProtein kinase AImmune systemCpG siteSignal transductionMolecular biologyImmunologyDNA methylationBiochemistryGene expression
MeSH Terms
AnimalsAntigen-Presenting CellsBone Marrow CellsCell LineCellsCulturedDendritic CellsDinucleoside PhosphatesGene Expression RegulationInterleukin-12LipopolysaccharidesLuciferasesMacrophagesMiceMiceInbred C57BLMitogen-Activated Protein KinasesOligodeoxyribonucleotidesRecombinant ProteinsThionucleotidesTransfectionTumor Necrosis Factor-alpha
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Publication Info
- Year
- 1999
- Type
- article
- Volume
- 18
- Issue
- 24
- Pages
- 6973-6982
- Citations
- 123
- Access
- Closed
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Cite This
H. Häcker
(1999).
Cell type-specific activation of mitogen-activated protein kinases by CpG-DNA controls interleukin-12 release from antigen-presenting cells.
The EMBO Journal
, 18
(24)
, 6973-6982.
https://doi.org/10.1093/emboj/18.24.6973
Identifiers
- DOI
- 10.1093/emboj/18.24.6973
- PMID
- 10601019
- PMCID
- PMC1171760