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The Journal of Immunology, Vol 150, Issue 12 5535-5543, Copyright © 1993 by American Association of Immunologists

ARTICLES

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

MA Brach, C Arnold, M Kiehntopf, HJ Gruss and F Herrmann
Department of Hematology, Oncology, and Applied Molecular Biology, Free University of Berlin, University Clinic Rudolf, Virchow, Germany.

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.


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