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Type 1 angiotensin receptors on macrophages ameliorate IL-1 receptor-mediated kidney fibrosis.

Publication ,  Journal Article
Zhang, J-D; Patel, MB; Griffiths, R; Dolber, PC; Ruiz, P; Sparks, MA; Stegbauer, J; Jin, H; Gomez, JA; Buckley, AF; Lefler, WS; Chen, D; Crowley, SD
Published in: J Clin Invest
May 2014

In a wide array of kidney diseases, type 1 angiotensin (AT1) receptors are present on the immune cells that infiltrate the renal interstitium. Here, we examined the actions of AT1 receptors on macrophages in progressive renal fibrosis and found that macrophage-specific AT1 receptor deficiency exacerbates kidney fibrosis induced by unilateral ureteral obstruction (UUO). Macrophages isolated from obstructed kidneys of mice lacking AT1 receptors solely on macrophages had heightened expression of proinflammatory M1 cytokines, including IL-1. Evaluation of isolated AT1 receptor-deficient macrophages confirmed the propensity of these cells to produce exaggerated levels of M1 cytokines, which led to more severe renal epithelial cell damage via IL-1 receptor activation in coculture compared with WT macrophages. A murine kidney crosstransplantation concomitant with UUO model revealed that augmentation of renal fibrosis instigated by AT1 receptor-deficient macrophages is mediated by IL-1 receptor stimulation in the kidney. This study indicates that a key role of AT1 receptors on macrophages is to protect the kidney from fibrosis by limiting activation of IL-1 receptors in the kidney.

Duke Scholars

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Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

May 2014

Volume

124

Issue

5

Start / End Page

2198 / 2203

Location

United States

Related Subject Headings

  • Ureteral Obstruction
  • Receptors, Interleukin-1
  • Receptor, Angiotensin, Type 1
  • Mice, Knockout
  • Mice
  • Macrophages
  • Kidney Diseases
  • Kidney
  • Interleukin-1
  • Immunology
 

Citation

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Zhang, J.-D., Patel, M. B., Griffiths, R., Dolber, P. C., Ruiz, P., Sparks, M. A., … Crowley, S. D. (2014). Type 1 angiotensin receptors on macrophages ameliorate IL-1 receptor-mediated kidney fibrosis. J Clin Invest, 124(5), 2198–2203. https://doi.org/10.1172/JCI61368
Zhang, Jian-dong, Mehul B. Patel, Robert Griffiths, Paul C. Dolber, Phillip Ruiz, Matthew A. Sparks, Johannes Stegbauer, et al. “Type 1 angiotensin receptors on macrophages ameliorate IL-1 receptor-mediated kidney fibrosis.J Clin Invest 124, no. 5 (May 2014): 2198–2203. https://doi.org/10.1172/JCI61368.
Zhang J-D, Patel MB, Griffiths R, Dolber PC, Ruiz P, Sparks MA, et al. Type 1 angiotensin receptors on macrophages ameliorate IL-1 receptor-mediated kidney fibrosis. J Clin Invest. 2014 May;124(5):2198–203.
Zhang, Jian-dong, et al. “Type 1 angiotensin receptors on macrophages ameliorate IL-1 receptor-mediated kidney fibrosis.J Clin Invest, vol. 124, no. 5, May 2014, pp. 2198–203. Pubmed, doi:10.1172/JCI61368.
Zhang J-D, Patel MB, Griffiths R, Dolber PC, Ruiz P, Sparks MA, Stegbauer J, Jin H, Gomez JA, Buckley AF, Lefler WS, Chen D, Crowley SD. Type 1 angiotensin receptors on macrophages ameliorate IL-1 receptor-mediated kidney fibrosis. J Clin Invest. 2014 May;124(5):2198–2203.

Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

May 2014

Volume

124

Issue

5

Start / End Page

2198 / 2203

Location

United States

Related Subject Headings

  • Ureteral Obstruction
  • Receptors, Interleukin-1
  • Receptor, Angiotensin, Type 1
  • Mice, Knockout
  • Mice
  • Macrophages
  • Kidney Diseases
  • Kidney
  • Interleukin-1
  • Immunology