IL-6 is required for renal JAK/STAT induction and hypertension during chronic angiotensin II (ANG II) infusion

Amy K Banes-Berceli, Hicham Labazi, Donald Cleghorn Jr, Michael W Brands

Research output: Contribution to journalConference abstractpeer-review

Abstract

ANG II is an established causative factor in many models of hypertension. However, recently it has been shown that there is a dependence of ANG II on the presence of interleukin-6 (IL-6) for full manifestation of its hypertensive effects. The molecular mechanisms for this dependence are as yet unknown. The Janus kinase 2 (JAK)/signal transducer of activated transcription (STAT) family is linked to both ANG II and IL-6; however, there has been no previous investigation of cross-talk between ANG II and IL-6 through this pathway. Therefore, we tested the hypothesis that activation of JAK2 is a critical intersection point in the ANG II/IL-6 signaling cascades. We utilized male C57 Black 6 (wild type, WT) mice and IL-6 Knockout (KO) mice and infused ANG II (90 ng/min) via osmotic mini-pumps. We measured mean arterial pressure (MAP) via telemetry and after 7 days of ANG II infusion the mice were euthanized and the kidneys were harvested. We isolated proteins and utilized standard Western techniques. ANG II treatment significantly increased MAP in both WT and IL-6 KO mice, however, WT-ANG II were significantly higher than the IL-6 KO-ANG II (WT-saline 113 ± 1.36, WT-ANG II 165 7.6, IL-6 KO saline 120 ± 2.0, IL-6 KO-ANG II 141 ± 10 mm Hg). ANG II treatment significantly increased the phosphorylated levels of JAK2 only in the WT mice (data reported as percentage of phospho/total, 25 ± 10.1, 77 ± 5.5, 26 ± 11.2, 30 ± 9.4, in WT-saline, WT-ANG II, IL-6 KO saline, IL-6 KO-ANG II, respectively). STAT-1 and STAT-3 phosphorylation levels were elevated only in the WT mice treated with ANG II. The phosphorylation levels of the related JAK family member, JAK1 was not different between WT and IL-6 KO mice and was not increased in either the WT or IL-6 KO mice by ANG II treatment. The phosphorylation levels of the critical docking protein SHP- were not different between WT and IL-6 KO mice and these levels were not significantly affected by ANG II treatment. There was no difference in the expression levels of JAK2, JAK1, STAT-3, STAT-1 and SHP-2 in any of the treatment groups. These data suggest that activation of the JAK2/STAT-1and STAT-3 pathway is critical for ANG II to fully manifest its hypertensive effect and that this is dependent on the presence of IL-6.
Original languageEnglish
Pages (from-to)E47-E47
Number of pages1
JournalHypertension
Volume52
Issue number4
DOIs
Publication statusPublished - 1 Oct 2008
Event62nd Annual High Blood Pressure Conference 2008 - Atlanta, United States
Duration: 17 Sept 200820 Sept 2008

Keywords

  • angiotensin II
  • hypertension
  • interleukin-6 (IL-6)

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