Regulation of NF-kappa B activation in T helper 1 and T helper 2 cells.
In most cell types, NF-kappa B is activated by release from a cytoplasmic inhibitor protein, I kappa B, followed by its translocation to the nucleus where it binds to the regulatory regions of many genes, including the IL-2 gene in T lymphocytes. We have previously shown by electrophoretic mobility shift assays that nuclear extracts prepared from activated, non-IL-2-producing Th2 cell clones. We show here that Th-1 and Th2 cells have similar levels of cytoplasmic p65(RelA) and p50, but TCR stimulation fails to induce the nuclear translocation of p65(RelA) in Th2 cells. Nuclear translocation of p65(RelA) can be induced by IL-1 stimulation of Th2 cells, indicating that a basic mechanism of NF-Kappa B activation common to many cells is intact in Th2 cells. We demonstrate that IL-1 and TNF induce rapid nuclear translocation of p65(RelA) in T cell clones, whereas TCR-induced NF-Kappa B activation in Th1 cells is delayed and may be longer in duration. This suggests that the TCR pathway of NF-Kappa B activation is different from the cytokine pathway. Furthermore, we show that Th1 and Th2 cells express different levels and/or different forms of I kappa B alpha, and that cytokines, but not TCR stimuli, significantly modulate detectable levels of cytoplasmic I kappa B alpha.
Lederer
J A
JA
Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Liou
J S
JS
Kim
S
S
Rice
N
N
Lichtman
A H
AH
D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000235:genetics; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D007376:Interleukin-2; D016328:NF-kappa B; D010750:Phosphoproteins; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C093915:lymphocyte-specific protein p50; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate