Regulation of GM-CSF expression by the transcription factor c-Maf.
BACKGROUND
Inflammation is a key feature of asthma and allergic disease. The proinflammatory cytokines IL-4, IL-5, and IL-13 are clustered on chromosome 5q with GM-CSF in close proximity, and each of these cytokines has been implicated in the pathogenesis of inflammatory disease. Although the expression of IL-4, IL-5, and IL-13 is coordinately regulated, the T(H)2-associated transcription factor c-Maf is thought to be involved only in the regulation of IL-4, the cytokine thought to be the main driver of T(H)2 differentiation.


OBJECTIVE
We sought to determine whether c-Maf influenced the expression of proinflammatory cytokines other than IL-4 in the Jurkat human T-cell line.


METHODS
RT-PCR, ELISA, and promoter-driven CAT assays were used to determine the effect of c-Maf overexpression on cytokine genes. A biotinylated oligo pulldown assay was used to demonstrate recruitment of c-Maf to the GM-CSF promoter.


RESULTS
We found that in addition to induction of IL-4, c-Maf could upregulate GM-CSF expression at both mRNA and protein levels, and that c-Maf could strongly activate the promoters of GM-CSF and IL-4 but not IL-5. Recruitment of c-Maf to the -33 to -97 bp region of the GM-CSF promoter was demonstrated.


CONCLUSIONS
We propose a novel role for c-Maf in the transcriptional regulation of GM-CSF in human T cells.


CONCLUSIONS
These data suggest that c-Maf may be a therapeutic target affecting both IL-4 and GM-CSF.
Gilmour
Jane
J
Medical Research Council and Asthma UK Center in Allergic Mechanisms of Asthma, King's College London, Guy's Hospital, London, UK.
Cousins
David J
DJ
Richards
David F
DF
Sattar
Zahid
Z
Lee
Tak H
TH
Lavender
Paul
P
D001483:Base Sequence; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D051257:Proto-Oncogene Proteins c-maf / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D015533:Transcriptional Activation; D015854:Up-Regulation
C495607:MAF protein, human; D051257:Proto-Oncogene Proteins c-maf; D012333:RNA, Messenger; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor