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Regulation of NRAMP1 gene expression by 1α,25‐dihydroxy‐vitamin D 3 in HL‐60 phagocytes
Author(s) -
Roig E. A.,
Richer E.,
CaneHergaux F.,
Gros P.,
Cellier M. F. M.
Publication year - 2002
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.71.5.890
Subject(s) - biology , microbiology and biotechnology , transcription (linguistics) , gene expression , messenger rna , promoter , regulation of gene expression , gene , biochemistry , philosophy , linguistics
The natural resistance‐associated macrophage protein 1 (Nramp1) is a proton‐dependent transporter of divalent metals. We studied NRAMP1 expression during HL‐60 differentiation induced by VD and VD agonists. NRAMP1 and CD14 gene expression differed in kinetics of induction, mRNA levels and stability, and response to VD combined with PMA, whereas a combination of VD and IFN‐γ induced similar up‐regulation. NRAMP1 protein expression paralleled the accumulation of mRNA and was localized in the phagosomal membrane after phagocytosis. A promoter construct extending 647 bp upstream of NRAMP1 ATG showed myeloid‐specific transcription in transient trasfection assays, which was up‐regulated by VD in HL‐60. In HL‐60 clones stably transfected with this construct, transcription was apparently induced through indirect VD genomic effects, and there was accordance between the levels of reporter transcription and endogenous NRAMP1 mRNA in response to VD but not to IFN‐γ. Thus, VD genomic effects stimulate NRAMP1 transcription and protein expression in maturing phagocytes.