Angiotensin II upregulates toll-like receptor 4 on mesangial cells.

Détails

ID Serval
serval:BIB_37AB51EADBB3
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Angiotensin II upregulates toll-like receptor 4 on mesangial cells.
Périodique
Journal of the American Society of Nephrology : Jasn
Auteur⸱e⸱s
Wolf G., Bohlender J., Bondeva T., Roger T., Thaiss F., Wenzel U.O.
ISSN
1046-6673 (Print)
ISSN-L
1046-6673
Statut éditorial
Publié
Date de publication
2006
Volume
17
Numéro
6
Pages
1585-1593
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Angiotensin II (AngII) mediates proinflammatory properties by activating NF-kappaB transcription factor nuclear translocation and inducing the expression of chemokines. For examination of whether AngII modulates the expression of Toll-like receptor 4 (TLR4), a key element of the innate immune system that senses LPS, mouse mesangial cells (MMC) were treated with AngII. AngII upregulated TLR4 mRNA and protein in MMC, and this effect was mediated through AngII type 1 receptors. Reporter gene experiments indicate that an activating protein-1 (AP-1) as well as an E-26 specific sequence (Ets) binding site in the TLR4 promoter are responsible for the AngII-stimulated transcriptional activity of the TLR4 gene. Preincubation of MMC with AngII enhanced LPS-induced NF-kappaB activation and chemokine expression. Immunohistochemical analyses revealed that double-transgenic rats that overexpressed human renin and angiotensinogen expressed higher levels of glomerular TLR4 compared with normal Sprague-Dawley rats. In vivo, infusion with AngII but not with norepinephrine into rats for 7 d also enhanced glomerular NF-kappaB activation after systemic application of LPS, suggesting that the effects are independent of concomitantly induced hypertension. Together, these observations suggest that AngII leads to an activation of the innate immune system by a novel mechanism involving the upregulation of TLR4. Our data contribute to a better understanding of how exogenous infections may trigger renal autoimmune processes, particularly in pathophysiologic situations with high renal AngII concentrations. Because TLR4 binds endogenous ligands (e.g., extracellular matrix components) in addition to microbial products, AngII-mediated upregulation of TLR4 also could be relevant for the development of inflammation in many noninfectious renal diseases.
Mots-clé
Angiotensin II/metabolism, Angiotensin II/physiology, Animals, Animals, Genetically Modified, Cell Line, Inflammation, Kidney Glomerulus/metabolism, Ligands, Lipopolysaccharides/metabolism, Mesangial Cells/cytology, Mice, NF-kappa B/metabolism, Rats, Rats, Wistar, Toll-Like Receptor 4/biosynthesis, Up-Regulation
Pubmed
Web of science
Open Access
Oui
Création de la notice
02/02/2008 11:17
Dernière modification de la notice
20/08/2019 14:26
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