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

Research output: Contribution to journalArticleResearchpeer-review

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

Cite this

Krishnan, S M ; Dowling, J K ; Ling, Y H ; Diep, H ; Chan, C T ; Ferens, D ; Kett, Michelle M ; Pinar, Anita ; Samuel, C S ; Vinh, A ; Arumugam, T V ; Hewitson, T D ; Kemp-Harper, B K ; Robertson, A A B ; Cooper, M A ; Latz, E ; Mansell, A ; Sobey, C G ; Drummond, G R. / Inflammasome activity is essential for one kidney/deoxycorticosterone acetate/salt-induced hypertension in mice. In: British Journal of Pharmacology. 2016 ; Vol. 173, No. 4. pp. 752-765.
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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",
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Inflammasome activity is essential for one kidney/deoxycorticosterone acetate/salt-induced hypertension in mice. / Krishnan, S M; Dowling, J K; Ling, Y H; Diep, H; Chan, C T; Ferens, D; Kett, Michelle M; Pinar, Anita; Samuel, C S; Vinh, A; Arumugam, T V; Hewitson, T D; Kemp-Harper, B K; Robertson, A A B; Cooper, M A; Latz, E; Mansell, A; Sobey, C G; Drummond, G R.

In: British Journal of Pharmacology, Vol. 173, No. 4, 01.02.2016, p. 752-765.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Inflammasome activity is essential for one kidney/deoxycorticosterone acetate/salt-induced hypertension in mice

AU - Krishnan, S M

AU - Dowling, J K

AU - Ling, Y H

AU - Diep, H

AU - Chan, C T

AU - Ferens, D

AU - Kett, Michelle M

AU - Pinar, Anita

AU - Samuel, C S

AU - Vinh, A

AU - Arumugam, T V

AU - Hewitson, T D

AU - Kemp-Harper, B K

AU - Robertson, A A B

AU - Cooper, M A

AU - Latz, E

AU - Mansell, A

AU - Sobey, C G

AU - Drummond, G R

PY - 2016/2/1

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N2 - 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

AB - 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

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DO - 10.1111/bph.13230

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VL - 173

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EP - 765

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 1476-5381

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