Coordinate NF-kappaB and STAT1 activation promotes development of myeloid type 1 dendritic cells

Scand J Immunol. 2008 Mar;67(3):260-9. doi: 10.1111/j.1365-3083.2007.02068.x.


NF-kappaB 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-kappaB and STAT1 in subsets of monocyte-derived dendritic cells (DC). Detailed kinetics and dose-response studies are presented for IL-1-, LPS-, CD40L-, IFN-gamma- and IFN-alpha-stimulated responses. The results are consistent with the notion that simultaneous activation of both STAT1 and NF-kappaB 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-kappaB and STAT1 distribution and response patterns. During the resting stage, DC differentiated under the presence of IFN-gamma showed sustained STAT activation and remained responsive to LPS. By contrast, PGE2-supplemented DC could be characterized by negligible responses to LPS and IFN-gamma and a remarkable NF-kappaB response to CD40L. STAT1 pathway was suppressed in PGE2-supplemented cells. We conclude that the magnitude and temporal kinetics of the nuclear shift of STAT1 and NF-kappaB 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / immunology*
  • Dendritic Cells / cytology*
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Enzyme Activation
  • Humans
  • Imaging, Three-Dimensional
  • Interleukin-12 / biosynthesis
  • Myeloid Cells / cytology
  • Myeloid Cells / immunology
  • Myeloid Cells / metabolism
  • NF-kappa B / metabolism*
  • Protein Transport / physiology
  • STAT1 Transcription Factor / metabolism*


  • NF-kappa B
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Interleukin-12