Differential expression of Rel/NF-kappaB and octamer factors is a hallmark of the generation and maturation of dendritic cells.
A key feature of maturation of dendritic cells is the down-regulation of antigen-processing and up-regulation of immunostimulatory capacities. To study the differential expression of transcription factors in this process, we investigated the nuclear translocation and DNA binding of Rel/NF-kappaB and octamer factors during in vitro generation and maturation of dendritic cells compared with macrophage development. RelB was the only factor strongly up-regulated during the generation of both immature dendritic cells and macrophages. Cytokine-induced maturation of dendritic cells resulted in an increase in nuclear RelB, p50, p52, and especially c-Rel, whereas cytokine-treated macrophages responded poorly. This up-regulation of NF-kappaB factors did not correlate with lower levels of cytosolic NF-kappaB inhibitors, the IkappaBs. One IkappaB, Bcl-3, was strongly expressed only in mature dendritic cells. Furthermore, generation and maturation of dendritic cells led to a continuous down-regulation of the octamer factor Oct-2, whereas monocytes and macrophages displayed high Oct-2 levels. A similar pattern of maturation-induced changes in transcription factor levels was found in cultured murine epidermal Langerhans cells, suggesting a general physiological significance of these findings. Finally, this pattern of differential activation of Rel and octamer factors appears to be suitable in determining the maturation stage of dendritic cells generated by treatment with different cytokine combinations in vitro. (Blood. 2000;95:277-285)
Neumann
M
M
Institute of Pathology, Department of Molecular Pathology, University of Würzburg, 97080 Würzburg, Germany.
Fries
H
H
Scheicher
C
C
Keikavoussi
P
P
Kolb-Mäurer
A
A
Bröcker
E
E
Serfling
E
E
Kämpgen
E
E
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000235:genetics*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D005786:Gene Expression Regulation / Q000276:immunology*; D051863:Host Cell Factor C1; D006801:Humans; D016130:Immunophenotyping; D007801:Langerhans Cells / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D050811:Octamer Transcription Factor-1; D050813:Octamer Transcription Factor-2; D011518:Proto-Oncogene Proteins / Q000235:genetics; D020569:Proto-Oncogene Proteins c-rel / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D051841:Transcription Factor RelB; D014157:Transcription Factors / Q000235:genetics*
D015703:Antigens, CD; D016207:Cytokines; D004268:DNA-Binding Proteins; C497692:HCFC1 protein, human; C497693:Hcfc1 protein, mouse; D051863:Host Cell Factor C1; D016328:NF-kappa B; D050811:Octamer Transcription Factor-1; D050813:Octamer Transcription Factor-2; C494165:POU2F1 protein, human; C058435:POU2F2 protein, human; C494166:Pou2f1 protein, mouse; C489206:Pou2f2 protein, mouse; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; C497593:RELB protein, human; D011994:Recombinant Proteins; C497594:Relb protein, mouse; D014157:Transcription Factors; D051841:Transcription Factor RelB