       Document 0075
 DOCN  M9630075
 TI    Inhibition of NF-AT-dependent transcription by NF-kappa B: implications
       for differential gene expression in T helper cell subsets.
 DT    9603
 AU    Casolaro V; Georas SN; Song Z; Zubkoff ID; Abdulkadir SA; Thanos D; Ono
       SJ; Department of Medicine, Johns Hopkins University, Baltimore, MD;
       21224, USA.
 SO    Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11623-7. Unique Identifier :
       AIDSLINE MED/96102166
 AB    Activation of individual CD4+ T cells results in differential lymphokine
       expression: interleukin 2 (IL-2) is preferentially produced by T helper
       type 1 (TH1) cells, which are involved in cell-mediated immune
       responses, whereas IL-4 is synthesized by TH2 cells, which are essential
       for humoral immunity. The Ca(2+)-dependent factor NF-ATp plays a key
       role in the inducible transcription of both these lymphokine genes.
       However, while IL2 expression requires the contribution of Ca(2+)- and
       protein kinase C-dependent signals, we report that activation of human
       IL4 transcription through the Ca(2+)-dependent pathway is diminished by
       protein kinase C stimulation in Jurkat T cells. This phenomenon is due
       to mutually exclusive binding of NF-ATp and NF-kappa B to the P
       sequence, an element located 69 bp upstream of the IL4 transcription
       initiation site. Human IL4 promoter-mediated transcription is
       downregulated in Jurkat cells stimulated with the NF-kappa B-activating
       cytokine tumor necrosis factor alpha and suppressed in
       RelA-overexpressing cells. In contrast, protein kinase C stimulation or
       RelA overexpression does not affect the activity of a human IL4 promoter
       containing a mouse P sequence, which is a higher-affinity site for
       NF-ATp and a lower-affinity site for RelA. Thus, competition between two
       general transcriptional activators, RelA and NF-ATp, mediates the
       inhibitory effect of protein kinase C stimulation on IL4 expression and
       may contribute to differential gene expression in TH cells.
 DE    Animal  Base Sequence  Cell Differentiation  DNA-Binding
       Proteins/*METABOLISM  *Gene Expression Regulation  Genes, Reporter
       Human  Interleukin-2/BIOSYNTHESIS/GENETICS
       Interleukin-4/BIOSYNTHESIS/GENETICS  Interleukins/*BIOSYNTHESIS/GENETICS
       Mice  Molecular Sequence Data  NF-kappa B/*METABOLISM  Promoter Regions
       (Genetics)  Protein Kinase C  Species Specificity  Support, Non-U.S.
       Gov't  Support, U.S. Gov't, P.H.S.  T-Lymphocyte Subsets
       T-Lymphocytes/*METABOLISM  Th1 Cells  Th2 Cells  Transcription
       Factors/*METABOLISM  *Transcription, Genetic  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

