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This Article Full Text Full Text (PDF) All Versions of this Article: 295/2/F446    most recent 00095.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Boesen, E. I. Articles by Pollock, D. M. Search for Related Content PubMed PubMed Citation Articles by Boesen, E. I. Articles by Pollock, D. M.

Interleukin-1β, but not interleukin-6, enhances renal and systemic endothelin production in vivo

¹Department of Pharmacology and Vascular Biology Center, Medical College of Georgia, Augusta, Georgia; and ²William Harvey Research Institute, London, United Kingdom

Submitted 22 February 2008 ; accepted in final form 4 June 2008

The inflammatory cytokines IL-1β and IL-6 have been shown to stimulate production of endothelin-1 (ET-1) by several cell types in vitro, but their effects on renal ET-1 production in vivo are not known. To test whether IL-1β and IL-6 stimulate renal ET-1 production and release in vivo, urine was collected from male C57BL/6 mice over 24-h periods at baseline and on days 7 and 14 of a 14-day subcutaneous infusion of IL-1β (10 ng/h), IL-6 (16 ng/h), or vehicle. By day 14, plasma ET-1 was significantly increased by IL-1β infusion (1.7 ± 0.1 vs. 0.8 ± 0.1 pg/ml for vehicle, P < 0.001). Compared with vehicle infusion, IL-1β infusion induced significant increases in urinary ET-1 excretion rate and urine flow but did not affect conscious mean arterial pressure (telemetry). IL-1β infusion significantly increased renal cortical and medullary IL-1β content (ELISA) and prepro-ET-1 mRNA expression (quantitative real-time PCR). In contrast, 14 days of IL-6 infusion had no significant effect on plasma ET-1 or urinary ET-1 excretion rate. To determine whether IL-1β stimulates ET-1 release via activation of NF-B, inner medullary collecting duct (IMCD-3) cells were incubated for 24 h with IL-1β, and ET-1 release and NF-B activation were measured (ELISA). IL-1β activated NF-B and increased ET-1 release in a concentration-dependent manner. The effect of IL-1β on ET-1 release could be partially inhibited by pretreatment of IMCD-3 cells with an inhibitor of NF-B activation (BAY 11-7082). These results indicate that IL-1β stimulates renal and systemic ET-1 production in vivo, providing further evidence that ET-1 participates in inflammatory responses.

renal inflammatory conditions; mouse inner medullary collecting duct cell line; nuclear factor-B; inflammatory cytokines