title: Chronic elevation of IL-1β induces diuresis via a cyclooxygenase 2-mediated mechanism.
abstract: Chronic renal inflammation is an increasingly recognized phenomenon in multiple disease states, but the impact of specific cytokines on renal function is unclear. Previously, we found that 14-day interleukin-1β (IL-1β) infusion increased urine flow in mice. To determine the mechanism by which this occurs, the current study tested the possible involvement of three classical prodiuretic pathways. Chronic IL-1β infusion significantly increased urine flow (6.5 ± 1 ml/day at day 14 vs. 2.3 ± 0.3 ml/day in vehicle group; P < 0.05) and expression of cyclooxygenase (COX)-2, all three nitric oxide synthase (NOS) isoforms, and endothelin (ET)-1 in the kidney (P < 0.05 in all cases). Urinary prostaglandin E metabolite (PGEM) excretion was also significantly increased at day 14 of IL-1β infusion (1.21 ± 0.26 vs. 0.29 ± 0.06 ng/day in vehicle-infused mice; P = 0.001). The selective COX-2 inhibitor celecoxib markedly attenuated urinary PGEM excretion and abolished the diuretic response to chronic IL-1β infusion. In contrast, deletion of NOS3, or inhibition of NOS1 with L-VNIO, did not blunt the diuretic effect of IL-1β, nor did pharmacological blockade of endothelin ETA and ETB receptors with A-182086. Consistent with a primary effect on water transport, IL-1β infusion markedly reduced inner medullary aquaporin-2 expression (P < 0.05) and did not alter urinary Na⁺ or K⁺ excretion. These data indicate a critical role for COX-2 in mediating the effects of chronic IL-1β elevation on the kidney.
authors: Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, USA. erika.boesen@unmc.edu
authors: E I
authors: EI
authors: Boesen
mesh_terms: D000818:Animals; D051399:Aquaporin 2 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000502:physiology*; D004231:Diuresis; D019332:Endothelin-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011458:Prostaglandins E / Q000378:metabolism
chemical_list: C496024:Aqp2 protein, mouse; D051399:Aquaporin 2; D019332:Endothelin-1; D053583:Interleukin-1beta; D011458:Prostaglandins E; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2
keywords: endothelin; kidney; nitric oxide synthase; prostaglandins