Transcriptional activation of the macrophage colony-stimulating factor gene by IL-2 is associated with secretion of bioactive macrophage colony-stimulating factor protein by monocytes and involves activation of the transcription factor NF-kappa B
Brach, M.A.; Arnold, C.; Kiehntopf, M.; Gruss, H.J.; Herrmann, F.
Journal of Immunology 150(12): 5535-5543
1993
ISSN/ISBN: 0022-1767 PMID: 8515075 Document Number: 414260
Human peripheral blood monocytes (Mo) constitutively display the beta-chain of the receptor for IL-2, whereas expression of the IL-2R alpha-chain is not constitutive but inducible with IL-2. Here we report that binding of human IL-2 to its binding site leads to transcriptional activation of the macrophage CSF (M-CSF) gene in Mo resulting in accumulation of M-CSF mRNA and subsequent release of bioactive M-CSF protein as demonstrated by ELISA and inhibition of IL-2 induced release of an activity-stimulating growth of monocyte-type colonies by a neutralizing anti-M-CSF antibody. Transcriptional activation of the M-CSF gene by IL-2 is preceded by enhanced binding activity of the transcription factor NF-kappa B to its recognition sequence in the 5' regulatory enhancer region of the M-CSF gene. Moreover, using a heterologous promoter (herpes thymidine kinase) construct containing the NF-kappa B consensus sequence, it is shown that NF-kappa B binding by an IL-2-induced monocyte-derived nuclear protein confers reporter gene (human growth hormone) activity. Taken together, our findings indicate that IL-2 induces gene expression of M-CSF in human blood-derived Mo and provide evidence for involvement of NF-kappa B in transcriptional regulation of this gene.