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Coordinate NF‐κB and STAT1 Activation Promotes Development of Myeloid Type 1 Dendritic Cells
Author(s) -
Vakkila J.,
Demarco R. A.,
Lotze M. T.
Publication year - 2008
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2007.02068.x
Subject(s) - cd40 , stat1 , nf κb , priming (agriculture) , microbiology and biotechnology , chemistry , nfkb1 , myeloid , stat , flow cytometry , biology , cancer research , signal transduction , immunology , transcription factor , in vitro , stat3 , biochemistry , gene , cytotoxic t cell , germination , botany
NF‐κB and STAT1 are critically involved in the initiation of the inflammatory cascade. Using semi‐automated imaging cytometry and fluorescent antibodies, we screened several factors for their ability to induce nuclear translocation of RelA/NF‐κB and STAT1 in subsets of monocyte‐derived dendritic cells (DC). Detailed kinetics and dose–response studies are presented for IL‐1‐, LPS‐, CD40L‐, IFN‐γ‐ and IFN‐α‐stimulated responses. The results are consistent with the notion that simultaneous activation of both STAT1 and NF‐κB pathways at the initiation of differentiation culture is required for efficient priming of IL‐12 production by DC. Maturation of DC led to characteristic NF‐κB and STAT1 distribution and response patterns. During the resting stage, DC differentiated under the presence of IFN‐γ showed sustained STAT activation and remained responsive to LPS. By contrast, PGE 2 ‐supplemented DC could be characterized by negligible responses to LPS and IFN‐γ and a remarkable NF‐κB response to CD40L. STAT1 pathway was suppressed in PGE 2 ‐supplemented cells. We conclude that the magnitude and temporal kinetics of the nuclear shift of STAT1 and NF‐κB in myeloid DC are associated with IL‐12p70 production and are dependent on the nature of the stimulating factors and the polarization state of cells.