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.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/156892
- author
- Lennartsson, Andreas LU ; Vidovic, Karina LU ; Pass, Malene Bjerregaard ; Cowland, Jack B and Gullberg, Urban LU
- organization
- publishing date
- 2006
- 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 & Sons Inc.
- 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
- 2022-01-26 08:56:07
@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}},
keywords = {{azurophil granule protein; granulocyte; innate immunity; transcriptional regulation}},
language = {{eng}},
number = {{1}},
pages = {{196--203}},
publisher = {{John Wiley & Sons Inc.}},
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}},
}