Hormonal control of the renal immune response and antibacterial host defense by arginine vasopressin.
Ascending urinary tract infection (UTI) and pyelonephritis caused by uropathogenic Escherichia coli (UPEC) are very common infections that can cause severe kidney damage. Collecting duct cells, the site of hormonally regulated ion transport and water absorption controlled by vasopressin, are the preferential intrarenal site of bacterial adhesion and initiation of inflammatory response. We investigated the effect of the potent V2 receptor (V2R) agonist deamino-8-D-arginine vasopressin (dDAVP) on the activation of the innate immune response using established and primary cultured collecting duct cells and an experimental model of ascending UTI. dDAVP inhibited Toll-like receptor 4-mediated nuclear factor kappaB activation and chemokine secretion in a V2R-specific manner. The dDAVP-mediated suppression involved activation of protein phosphatase 2A and required an intact cystic fibrosis transmembrane conductance regulator Cl- channel. In vivo infusion of dDAVP induced a marked fall in proinflammatory mediators and neutrophil recruitment, and a dramatic rise in the renal bacterial burden in mice inoculated with UPECs. Conversely, administration of the V2R antagonist SR121463B to UPEC-infected mice stimulated both the local innate response and the antibacterial host defense. These findings evidenced a novel hormonal regulation of innate immune cellular activation and demonstrate that dDAVP is a potent modulator of microbial-induced inflammation in the kidney.
Chassin
Cécilia
C
Institut National de la Santé et de la Recherche Médicale, U773, Centre de Recherche Biomédicale Bichat-Beaujon, BP 416, 75018 Paris, France.
Hornef
Mathias W
MW
Bens
Marcelle
M
Lotz
Michael
M
Goujon
Jean-Michel
JM
Vimont
Sophie
S
Arlet
Guillaume
G
Hertig
Alexandre
A
Rondeau
Eric
E
Vandewalle
Alain
A
D000328:Adult; D000818:Animals; D001127:Arginine Vasopressin / Q000502:physiology*; D002648:Child; D004927:Escherichia coli Infections / Q000276:immunology; D006801:Humans; D016030:Kidney Transplantation; D007685:Kidney Tubules, Collecting / Q000276:immunology / Q000502:physiology*; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014552:Urinary Tract Infections / Q000276:immunology*; D019459:Urothelium / Q000276:immunology / Q000502:physiology
D008070:Lipopolysaccharides; C495345:TLR4 protein, human; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D001127:Arginine Vasopressin