Article (Scientific journals)
Importance of post-transcriptional regulation of chemokine genes by oxidative stress.
JOSSE, Claire; Boelaert, J. R.; Best-Belpomme, M. et al.
2001In Biochemical Journal, 360 (Pt 2), p. 321-33
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Keywords :
Cell-Free System/drug effects/secretion; Chemokine CCL2/genetics/metabolism; Chemokines/biosynthesis/genetics/metabolism; Enzyme Activation/genetics; Gene Expression Regulation/drug effects; Humans; Hydrogen Peroxide/pharmacology; Interleukin-8/genetics/metabolism/secretion; Mitogen-Activated Protein Kinases/metabolism; NF-kappa B/metabolism; Oxidative Stress/drug effects/genetics; Promoter Regions, Genetic; Protein Binding/genetics; RNA Processing, Post-Transcriptional/drug effects; RNA, Messenger/biosynthesis/metabolism; Transcription, Genetic/drug effects; Tumor Cells, Cultured; U937 Cells/drug effects/secretion; p38 Mitogen-Activated Protein Kinases
Abstract :
[en] The transcription factor, nuclear factor kappa B (NF-kappa B), is activated by various stimuli including cytokines, radiation, viruses and oxidative stress. Here we show that, although induction with H(2)O(2) gives rise to NF-kappa B nuclear translocation in both lymphocyte (CEM) and monocyte (U937) cells, it leads only to the production of mRNA species encoding interleukin-8 (IL-8) and macrophage inflammatory protein 1 alpha in U937 cells. Under similar conditions these mRNA species are not observed in CEM cells. With the use of a transient transfection assay of U937 cells transfected with reporter constructs of the IL-8 promoter and subsequently treated with H(2)O(2), we show that (1) IL-8-promoter-driven transcription is stimulated in both U937 and CEM cells and (2) the NF-kappa B site is crucial for activation because its deletion abolishes activation by H(2)O(2). The production of IL-8 mRNA in U937 cells is inhibited by the NF-kappa B inhibitors clasto-lactacystin-beta-lactone and E-64D (l-3-trans-ethoxycarbonyloxirane-2-carbonyl-L-leucine-3-methyl amide) but requires protein synthesis de novo. Moreover, inhibition of the p38 mitogen-activated protein kinase also decreases the IL-8 mRNA up-regulation mediated by H(2)O(2). Taken together, these results show the importance of post-transcriptional events controlled by a p38-dependent pathway in the production of IL-8 mRNA in U937. The much lower activation of p38 in CEM cells in response to H(2)O(2) could explain the lack of stabilization of IL-8 mRNA in these cells.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
JOSSE, Claire  ;  Centre Hospitalier Universitaire de Liège - CHU > Oncologie médicale
Boelaert, J. R.
Best-Belpomme, M.
Piette, Jacques ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Virologie - Immunologie
Language :
English
Title :
Importance of post-transcriptional regulation of chemokine genes by oxidative stress.
Publication date :
2001
Journal title :
Biochemical Journal
ISSN :
0264-6021
eISSN :
1470-8728
Publisher :
Portland Press, United Kingdom
Volume :
360
Issue :
Pt 2
Pages :
321-33
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 11 August 2014

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