| First Author | Boesen EI | Year | 2013 |
| Journal | Am J Physiol Renal Physiol | Volume | 305 |
| Issue | 2 | Pages | F189-98 |
| PubMed ID | 23657858 | Mgi Jnum | J:323087 |
| Mgi Id | MGI:6877600 | Doi | 10.1152/ajprenal.00075.2013 |
| Citation | Boesen EI (2013) Chronic elevation of IL-1beta induces diuresis via a cyclooxygenase 2-mediated mechanism. Am J Physiol Renal Physiol 305(2):F189-98 |
| abstractText | 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-1beta (IL-1beta) 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-1beta 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-1beta 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-1beta infusion. In contrast, deletion of NOS3, or inhibition of NOS1 with L-VNIO, did not blunt the diuretic effect of IL-1beta, nor did pharmacological blockade of endothelin ETA and ETB receptors with A-182086. Consistent with a primary effect on water transport, IL-1beta 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-1beta elevation on the kidney. |
