Dataset Information

Hormonal control of the renal immune response and antibacterial host defense by arginine vasopressin.

ABSTRACT: 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.

SUBMITTER: Chassin C

PROVIDER: S-EPMC2118508 | biostudies-literature | 2007 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Hormonal control of the renal immune response and antibacterial host defense by arginine vasopressin.

Chassin Cécilia C 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

The Journal of experimental medicine 20071029 12

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 ...[more]

PMID: 17967904

Similar Datasets

Project description:Arginine vasopressin (AVP), a hormone secreted by the posterior pituitary, plays a vital role in maintaining vasomotor tone during acute blood loss. We hypothesized that decompensated hemorrhagic shock is associated with decreased AVP stores and supplementation during resuscitation would improve both blood pressure and renal function. Using a decompensated hemorrhagic shock model, male Long-Evans rats were bled to mean arterial blood pressure (MAP) of 40mmHg and maintained until the MAP could not be sustained without fluid. Once 40% of the shed volume was returned in lactated Ringer's (Severe Shock), animals were resuscitated over 60 minutes with 4x the shed volume in lactated Ringer's (LR) or the same fluids with AVP (0.5 units/kg+ 0.03 units/kg/min). Animals (n = 6-9/group) were sacrificed before hemorrhage (Sham), at Severe Shock, following resuscitation (60R, 60R with AVP) or 18 hours post-resuscitation (18hr, 18hr with AVP). Blood samples were taken to measure AVP levels and renal function. Pituitaries were harvested and assayed for AVP. Kidney samples were taken to assess mitochondrial function, histology, and oxidative damage. Baseline pituitary AVP stores (30,364 ± 5311 pg/mg) decreased with severe shock and were significantly depressed post-resuscitation (13,910 ± 3016 pg/ml. p<0.05) and at 18hr (15,592 ±1169 pg/ml, p<0.05). Resuscitation with LR+AVP led to higher serum AVP levels at 60R (31±8 vs 79±12; p<0.01) with an improved MAP both at 60R (125±3 vs 77±7mmHg; p<0.01) and 18hr (82±6 vs 69±5mmHg;p<0.05). AVP supplementation preserved complex I respiratory capacity at 60R and both complex I and II function at 18hr (p<0.05). AVP was also associated with decreased reactive oxygen species at 60R (856±67 vs 622±48F RFU) and significantly decreased oxidative damage as measured by mitochondrial lipid peroxidation (0.9±0.1 vs 1.7±0.1 fold change, p<0.01) and nitrosylation (0.9±0.1 vs 1.4±0.2 fold change, p<0.05). With AVP, renal damage was mitigated at 60R and histologic architecture was conserved at 18 hours. In conclusion, pituitary and serum AVP levels decrease during severe hemorrhage and may contribute to the development of decompensated hemorrhagic shock. Supplementing exogenous AVP during resuscitation improves blood pressure, preserves renal mitochondrial function, and mitigates acute kidney injury.

Dataset Information

Hormonal control of the renal immune response and antibacterial host defense by arginine vasopressin.

Publications

Hormonal control of the renal immune response and antibacterial host defense by arginine vasopressin.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets