Inflammasome activity is essential for one kidney/deoxycorticosterone acetate/salt-induced hypertension in mice

S M Krishnan, J K Dowling, Y H Ling, H Diep, C T Chan, D Ferens, Michelle M Kett, Anita Pinar, C S Samuel, A Vinh, T V Arumugam, T D Hewitson, B K Kemp-Harper, A A B Robertson, M A Cooper, E Latz, A Mansell, C G Sobey, G R Drummond

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Abstract

BACKGROUND AND PURPOSE: Inflammasomes are multimeric complexes that facilitate caspase-1-mediated processing of the pro-inflammatory cytokines interleukin(IL)-1beta and IL-18. Clinical hypertension is associated with renal inflammation, and elevated circulating levels of IL-1beta and IL-18. Therefore, we investigated whether hypertension in mice is associated with increased expression and/or activation of the inflammasome in the kidney, and if inhibition of inflammasome activity reduces blood pressure (BP), markers of renal inflammation and fibrosis. EXPERIMENTAL APPROACH: Wild-type and inflammasome-deficient ASC-/- mice were uninephrectomised and received deoxycorticosterone acetate and saline to drink (1K/DOCA/salt). Control mice were uninephrectomised and received placebo and water. BP was measured by tail cuff; renal expression of inflammasome subunits and inflammatory markers was measured by real-time PCR and immunoblotting; macrophage and collagen accumulation was assessed by immunohistochemistry. KEY RESULTS: 1K/DOCA/salt-induced hypertension in mice was associated with increased renal mRNA expression (fold-change vs control; P
Original languageEnglish
Pages (from-to)752-765
Number of pages14
JournalBritish Journal of Pharmacology
Volume173
Issue number4
DOIs
Publication statusPublished - 1 Feb 2016

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