TY - JOUR
T1 - Interleukin-1β, but not interleukin-6, enhances renal and systemic endothelin production in vivo
AU - Boesen, Erika I.
AU - Sasser, Jennifer M.
AU - Saleh, Mohamed A.
AU - Potter, William A.
AU - Woods, Mandy
AU - Warner, Timothy D.
AU - Pollock, Jennifer S.
AU - Pollock, David M.
PY - 2008/8
Y1 - 2008/8
N2 - 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-κB, inner medullary collecting duct (IMCD-3) cells were incubated for 24 h with IL-1β, and ET-1 release and NF-κB activation were measured (ELISA). IL-1β activated NF-κB 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-κB 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.
AB - 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-κB, inner medullary collecting duct (IMCD-3) cells were incubated for 24 h with IL-1β, and ET-1 release and NF-κB activation were measured (ELISA). IL-1β activated NF-κB 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-κB 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.
KW - Inflammatory cytokines
KW - Mouse inner medullary collecting duct cell line
KW - Nuclear factor-κB
KW - Renal inflammatory conditions
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U2 - 10.1152/ajprenal.00095.2008
DO - 10.1152/ajprenal.00095.2008
M3 - Article
C2 - 18524861
AN - SCOPUS:52449126954
SN - 1931-857X
VL - 295
SP - F446-F453
JO - American Journal of Physiology - Renal Physiology
JF - American Journal of Physiology - Renal Physiology
IS - 2
ER -