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All-trans retinoic acid-induced expression of bactericidal/permeability-increasing protein (BPI) in human myeloid cells correlates to binding of C/EBP{beta} and C/EBP{varepsilon} to the BPI promoter.

Lennartsson, Andreas LU ; Vidovic, Karina LU ; Pass, Malene Bjerregaard ; Cowland, Jack B and Gullberg, Urban LU (2006) In Journal of Leukocyte Biology 80(1). p.196-203
Abstract
Bactericidal/permeability-inereasing protein (BPI) neutralizes the proinflammatory effects of lipopolysaccharide and is of potential clinical use in the treatment of fulminant Gram-negative infections. BPI is a cationic protein with antibacterial activity stored in azurophil (primary) granules of neutrophil granulocytes. However, the absence of BPI in patients with specific granule deficiency indicates a transcriptional control of BPI, which is distinct from that of other azurophil granule proteins. Accordingly, we demonstrate in vivo that the BPI mRNA level peaks, together with mRNA for specific granule proteins, during the myelocytic and metamyelocytic stage of granulocytic maturation. The human promyelocytic cell line NB4 expresses... (More)
Bactericidal/permeability-inereasing protein (BPI) neutralizes the proinflammatory effects of lipopolysaccharide and is of potential clinical use in the treatment of fulminant Gram-negative infections. BPI is a cationic protein with antibacterial activity stored in azurophil (primary) granules of neutrophil granulocytes. However, the absence of BPI in patients with specific granule deficiency indicates a transcriptional control of BPI, which is distinct from that of other azurophil granule proteins. Accordingly, we demonstrate in vivo that the BPI mRNA level peaks, together with mRNA for specific granule proteins, during the myelocytic and metamyelocytic stage of granulocytic maturation. The human promyelocytic cell line NB4 expresses several azurophil granule proteins, but expression of BPI is undetectable. We show that treatment of NB4 cells with all-trans retinoic acid (ATRA) induces BPI expression at mRNA and at protein level. The induction is dependent on de novo protein synthesis, as judged by sensitivity to cycloheximide. Previous investigations have indicated a potential role of CCAAT/enhancer-binding protein (C/EBP) transcription factors in the regulation of BPI expression. Here, we show that induction of NB4 cells with ATRA correlates to direct binding of C/EBP beta and C/EBP epsilon to the proximal BPI promoter, as determined by electrophoretic mobility shift analysis and chromatin immunoprecipitation. The dependency on C/EBP beta and C/EBP epsilon provides an explanation for delayed BPI mRNA expression, as compared with mRNA of other azurophil granule proteins. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
azurophil granule protein, granulocyte, innate immunity, transcriptional regulation
in
Journal of Leukocyte Biology
volume
80
issue
1
pages
196 - 203
publisher
John Wiley and Sons Ltd
external identifiers
  • wos:000243015500021
  • scopus:33751509411
ISSN
1938-3673
DOI
10.1189/jlb.1205759
language
English
LU publication?
yes
id
b93d2363-30b7-4fe8-a511-ba3e409ba8cf (old id 156892)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16684888&dopt=Abstract
date added to LUP
2016-04-01 11:42:08
date last changed
2020-01-12 08:26:16
@article{b93d2363-30b7-4fe8-a511-ba3e409ba8cf,
  abstract     = {Bactericidal/permeability-inereasing protein (BPI) neutralizes the proinflammatory effects of lipopolysaccharide and is of potential clinical use in the treatment of fulminant Gram-negative infections. BPI is a cationic protein with antibacterial activity stored in azurophil (primary) granules of neutrophil granulocytes. However, the absence of BPI in patients with specific granule deficiency indicates a transcriptional control of BPI, which is distinct from that of other azurophil granule proteins. Accordingly, we demonstrate in vivo that the BPI mRNA level peaks, together with mRNA for specific granule proteins, during the myelocytic and metamyelocytic stage of granulocytic maturation. The human promyelocytic cell line NB4 expresses several azurophil granule proteins, but expression of BPI is undetectable. We show that treatment of NB4 cells with all-trans retinoic acid (ATRA) induces BPI expression at mRNA and at protein level. The induction is dependent on de novo protein synthesis, as judged by sensitivity to cycloheximide. Previous investigations have indicated a potential role of CCAAT/enhancer-binding protein (C/EBP) transcription factors in the regulation of BPI expression. Here, we show that induction of NB4 cells with ATRA correlates to direct binding of C/EBP beta and C/EBP epsilon to the proximal BPI promoter, as determined by electrophoretic mobility shift analysis and chromatin immunoprecipitation. The dependency on C/EBP beta and C/EBP epsilon provides an explanation for delayed BPI mRNA expression, as compared with mRNA of other azurophil granule proteins.},
  author       = {Lennartsson, Andreas and Vidovic, Karina and Pass, Malene Bjerregaard and Cowland, Jack B and Gullberg, Urban},
  issn         = {1938-3673},
  language     = {eng},
  number       = {1},
  pages        = {196--203},
  publisher    = {John Wiley and Sons Ltd},
  series       = {Journal of Leukocyte Biology},
  title        = {All-trans retinoic acid-induced expression of bactericidal/permeability-increasing protein (BPI) in human myeloid cells correlates to binding of C/EBP{beta} and C/EBP{varepsilon} to the BPI promoter.},
  url          = {http://dx.doi.org/10.1189/jlb.1205759},
  doi          = {10.1189/jlb.1205759},
  volume       = {80},
  year         = {2006},
}