, Volume 38, Issue 4, pp 1690–1699 | Cite as

Stimulation of the Angiotensin II AT2 Receptor is Anti-inflammatory in Human Lipopolysaccharide-Activated Monocytic Cells

  • Mario MenkEmail author
  • Jan Adriaan Graw
  • Clarissa von Haefen
  • Marco Sifringer
  • David Schwaiberger
  • Thomas Unger
  • Ulrike Steckelings
  • Claudia D. Spies


Recently, AT2 receptors have been discovered on the surface of human immunocompetent cells such as monocytes. Data on regulative properties of this receptor on the cellular immune response are poor. We hypothesized that direct stimulation of the AT2 receptor mediates anti-inflammatory responses in these cells. Human monocytic THP-1 and U937 cells were stimulated with lipopolysaccharide (LPS) and the selective AT2 receptor agonist Compound 21 (C21). Expression of pro- and anti-inflammatory cytokines IL-6, IL-10, tumor necrosis factor-α (TNFα), and IL-1β were analyzed on both the transcriptional and the translational level over course of time. Treatment with C21 attenuated the expression of TNFα, IL-6, and IL-10 after LPS challenge in both cell lines in a time- and dose-dependent manner. We conclude that selective AT2 receptor stimulation acts anti-inflammatory in human monocytes. Modulation of cytokine response by AT2 receptor activation might be a beneficial and novel treatment concept in inflammatory conditions.


AT2 receptor Compound 21 (C21) THP-1 cells inflammation monocytes 


Compliance with Ethical Standards

UMS received modest research support from Vicore Pharma (short-term fellowship and free drug supply). All other authors do not have potential conflicts of interest. Research did not involve human participants or animals and strictly followed the rules of good scientific practice.


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Mario Menk
    • 1
    Email author
  • Jan Adriaan Graw
    • 1
  • Clarissa von Haefen
    • 1
  • Marco Sifringer
    • 1
  • David Schwaiberger
    • 1
  • Thomas Unger
    • 2
  • Ulrike Steckelings
    • 3
  • Claudia D. Spies
    • 1
  1. 1.Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte and Campus Virchow-KlinikumCharité—Universitätsmedizin BerlinBerlinGermany
  2. 2.CARIM, School for Cardiovascular DiseasesMaastricht UniversityMaastrichtThe Netherlands
  3. 3.Department of Cardiovascular and Renal ResearchUniversity of Southern DenmarkOdenseDenmark

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