title: Stimulation of the Angiotensin II AT2 Receptor is Anti-inflammatory in Human Lipopolysaccharide-Activated Monocytic Cells.
abstract: 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.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte and Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany, mario.menk@charite.de.
authors.forename: Mario
authors.initials: M
authors.lastname: Menk
authors.forename: Jan Adriaan
authors.initials: JA
authors.lastname: Graw
authors.forename: Clarissa
authors.initials: C
authors.lastname: von Haefen
authors.forename: Marco
authors.initials: M
authors.lastname: Sifringer
authors.forename: David
authors.initials: D
authors.lastname: Schwaiberger
authors.forename: Thomas
authors.initials: T
authors.lastname: Unger
authors.forename: Ulrike
authors.initials: U
authors.lastname: Steckelings
authors.forename: Claudia D
authors.initials: CD
authors.lastname: Spies
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000819:agonists* / Q000096:biosynthesis*; D020298:U937 Cells
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D044139:Receptor, Angiotensin, Type 2