Effects of IL-3 and LPS on transcription factors involved in the regulation of IL-6 mRNA.
Recently it has been demonstrated that in vivo application of interleukin-3 (IL-3) is associated with the release of IL-6. This observation suggests that the transcription factors triggered by IL-3 are in great homology with the transcription factors induced by lipopolysaccharide (LPS). The results of the present study with in vitro activated human monocytes demonstrate that IL-3 alone is incapable of inducing IL-6 mRNA, but primes monocytes to enhance the IL-6 mRNA expression when co-stimulated with LPS. The difference in effect between IL-3 and LPS might be related to our observation that IL-3 induces the p5O subunit of the transcription factor nuclear factor-kappa B (NF-Kappa B), whereas LPS appears to induce both the p5O as well as the p65 subunit of NF-kappa B, as demonstrated with RNA studies and electrophoretic mobility shift assays (EMSA). However, no difference was found with regard to the induction of activator protein-1 (AP-1) and NF-IL6 after treatment with IL-3 or LPS alone. Priming with IL-3 followed by LPS stimulation is associated with a reduced expression of NF-kappa B without changing the composition of the complex. In addition, a reduced expression of c-fos and c-jun mRNA was noticed, combined with a reduced DNA binding activity of AP-1. However, the expression of NF-IL6 was enhanced when priming with IL-3 followed by LPS. Since AP-1 has been suggested as negative regulator of the IL-6 gene expression, it is conceivable that, after priming with IL-3, the reduced DNA binding activity of AP-1, in conjunction with the increased DNA binding of NF-IL6, might result in a synergistic effect on IL-6 mRNA expression, when compared to stimulation with LPS alone.
Tuyt
L M
LM
Department of Haematology, University of Groningen, The Netherlands.
De Wit
H
H
Koopmans
S B
SB
Sierdsema
S J
SJ
Vellenga
E
E
D001483:Base Sequence; D015152:Blotting, Northern; D016762:Genes, fos; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000502:physiology; D018809:Proliferating Cell Nuclear Antigen / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics*
D007377:Interleukin-3; D015850:Interleukin-6; D008070:Lipopolysaccharides; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger