期刊
SCANDINAVIAN JOURNAL OF IMMUNOLOGY
卷 67, 期 3, 页码 260-269出版社
WILEY
DOI: 10.1111/j.1365-3083.2007.02068.x
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- NCI NIH HHS [1 P01 CA 101944-01A2] Funding Source: Medline
NF-kappa B 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-kappa B 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-kappa B 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-kappa B 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, PGE(2)-supplemented DC could be characterized by negligible responses to LPS and IFN-gamma and a remarkable NF-kappa B 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-kappa B 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.
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