Corticotropin-releasing factor and the urocortins induce the expression of TLR4 in macrophages via activation of the transcription factors PU.1 and AP-1.

Détails

ID Serval
serval:BIB_74C8564C5583
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Corticotropin-releasing factor and the urocortins induce the expression of TLR4 in macrophages via activation of the transcription factors PU.1 and AP-1.
Périodique
Journal of Immunology
Auteur(s)
Tsatsanis C., Androulidaki A., Alissafi T., Charalampopoulos I., Dermitzaki E., Roger T., Gravanis A., Margioris A.N.
ISSN
0022-1767 (Print)
ISSN-L
0022-1767
Statut éditorial
Publié
Date de publication
2006
Volume
176
Numéro
3
Pages
1869-1877
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Résumé
Corticotropin-releasing factor (CRF) augments LPS-induced proinflammatory cytokine production from macrophages. The aim of the present study was to determine the mechanism by which CRF and its related peptides urocortins (UCN) 1 and 2 affect LPS-induced cytokine production. We examined their role on TLR4 expression, the signal-transducing receptor of LPS. For this purpose, the murine macrophage cell line RAW 264.7 and primary murine peritoneal macrophages were used. Exposure of peritoneal macrophages and RAW 264.7 cells to CRF, UCN1, or UCN2 up-regulated TLR4 mRNA and protein levels. To study whether that effect occurred at the transcriptional level, RAW 264.7 cells were transfected with a construct containing the proximal region of the TLR4 promoter linked to the luciferase gene. CRF peptides induced activation of the TLR4 promoter, an effect abolished upon mutation of a proximal PU.1-binding consensus or upon mutation of an AP-1-binding element. Indeed, all three peptides promoted PU.1 binding to the proximal PU.1 site and increased DNA-binding activity to the AP-1 site. The effects of CRF peptides were inhibited by the CRF2 antagonist anti-sauvagine-30, but not by the CRF1 antagonist antalarmin, suggesting that CRF peptides mediated the up-regulation of TLR4 via the CRF2 receptor. Finally, CRF peptides blocked the inhibitory effect of LPS on TLR4 expression. In conclusion, our data suggest that CRF peptides play an important role on macrophage function. They augment the effect of LPS by inducing Tlr4 gene expression, through CRF2, via activation of the transcription factors PU.1 and AP-1.
Mots-clé
Animals, Cell Line, Corticotropin-Releasing Hormone/physiology, Gene Expression Regulation/immunology, Genes, Reporter, Lipopolysaccharides/metabolism, Macrophages/metabolism, Mice, Peptide Fragments/physiology, Promoter Regions, Genetic, Proto-Oncogene Proteins/metabolism, Proto-Oncogene Proteins/physiology, Receptors, Corticotropin-Releasing Hormone/metabolism, Toll-Like Receptor 4/biosynthesis, Toll-Like Receptor 4/genetics, Trans-Activators/metabolism, Trans-Activators/physiology, Transcription Factor AP-1/metabolism, Transcription Factor AP-1/physiology, Transfection, Urocortins
Pubmed
Web of science
Création de la notice
02/02/2008 11:00
Dernière modification de la notice
03/03/2018 18:22
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