The NF kappa B heterodimer/homodimer balance and IL-1-stimulated IL-2 production in murine T lymphocytes.
Activation of NF kappa B is considered one way IL-1 exerts its costimulatory effect on T cell activation and IL-2 production. However, T helper 2 cells do not synthesize IL-2 upon IL-1 stimulation, although they depend on IL-1 for proliferation. The involvement of NF kappa B in IL-2 production was therefore addressed in two different murine cell lines: D10N, a T helper 2 cell line that does not synthesize IL-2, and EL4 6.1., a thymoma cell line producing IL-2 when stimulated with IL-1. In both cell types IL-1 activated the DNA binding activity of the NF kappa B heterodimers p50/65 and p50/c-rel via the IL-1 type I receptor. In D10N cells, however, the p50/p50 homodimer is present in large amounts in unstimulated cells, whereas the heterodimers were only activated by IL-1-treatment. In contrast, only marginal amounts of the p50/p50 homodimer were found in EL4 6.1. cells, but a strong activation of heterodimers was induced by IL-1. The findings are compatible with the concept of p50 homodimer being inhibitory by replacing the p50/p65 or p50/c-rel heterodimer from nuclear kappa B binding sites. The inability of D10N cells to respond to IL-1 exposure with IL-2 formation might therefore be due to their high constitutive levels of p50 homodimers.
Brigelius-Flohé
R
R
Institute of Molecular Pharmacology, Medical School Hannover, Germany. Regina.Flohe@ERN.dife.d400.de
Bilgin
B
B
Eickemeier
S
S
Hipskind
R
R
Singh
M
M
Szamel
M
M
Resch
K
K
D000818:Animals; D002460:Cell Line; D003432:Cross-Linking Reagents; D004247:DNA / Q000378:metabolism; D019281:Dimerization; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis*; D046911:Macromolecular Substances; D051379:Mice; D016328:NF-kappa B / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000502:physiology; D011994:Recombinant Proteins; D012795:Sialoglycoproteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000378:metabolism*
D003432:Cross-Linking Reagents; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D007376:Interleukin-2; D046911:Macromolecular Substances; D016328:NF-kappa B; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D004247:DNA