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 κB 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.
Hormonal control of the renal immune response and antibacterial host defense by arginine vasopressin
Abbreviations used: AVP, arginine vasopressin; cAMP, cyclic AMP; CCD, cortical collecting duct; CFTR, cystic fibrosis transmembrane conductance regulator; dDAVP, deamino-8-D-AVP; ENaC, epithelial sodium channel; Gly, glybenclamide; ICAM, intracellular adhesion molecule; MIP-2, macrophage inflammatory protein 2; MPO, myeloperoxydase; MyD88. myeloid differentiation factor 88; NPPB, 5-nitro-2(3phenylpropyl-amino)benzoate; PKA, protein kinase A; PP1 and PP2A, protein phosphatase 1 and 2A, respectively; RANTES, regulated on activation, normal T cell expressed and secreted; Ser/Thr, serine/threonine; siRNA, small-interfering RNA; TLR, Toll-like receptor; UPEC, uropathogenic Escherichia coli; UTI, urinary tract infection; V2R, V2 receptor.
Cécilia Chassin, Mathias W. Hornef, Marcelle Bens, Michael Lotz, Jean-Michel Goujon, Sophie Vimont, Guillaume Arlet, Alexandre Hertig, Eric Rondeau, Alain Vandewalle; Hormonal control of the renal immune response and antibacterial host defense by arginine vasopressin . J Exp Med 26 November 2007; 204 (12): 2837–2852. doi: https://doi.org/10.1084/jem.20071032
Download citation file:
Sign in
Client Account
Sign in via your Institution
Sign in via your InstitutionEmail alerts
Advertisement