Angiotensin II type-2 receptors modulate inflammation through signal transducer and activator of transcription proteins 3 phosphorylation and TNFα production

Peter M. Abadir, Jeremy D. Walston, Robert M. Carey, Helmy M. Siragy

Research output: Contribution to journalArticlepeer-review

Abstract

Angiotensin subtype-1 receptor (AT1R) influences inflammatory processes through enhancing signal transducer and activator of transcription proteins 3 (STAT3) signal transduction, resulting in increased tumor necrosis factor-α (TNF-α) production. Although angiotensin subtype-2 receptor (AT2R), in general, antagonizes AT1R-stimulated activity, it is not known if AT2R has any anti-inflammatory effects. In this study, we tested the hypothesis that AT2R activation plays an anti-inflammatory role by reducing STAT3 phosphorylation and TNF-α production. Changes in AT2R expression, TNF-α production, and STAT3 phosphorylation were quantified by Western blotting, Bio-Plex cytokine, and phosphoprotein cellular signaling assays in PC12W cells that express AT 2R but not AT1R, in response to the AT2R agonist, CGP-42112 (CGP, 100nm), or AT2R antagonist PD-123319 (PD, 1 μm). A 100% increase in AT2R expression in response to stimulation with its agonist CGP was observed. Further, AT2R activation reduced TNF-a production by 39% and STAT3 phosphorylation by 83%. In contrast, PD decreased AT2R expression by 76%, increased TNF-α production by 84%, and increased STAT3 phosphorylation by 67%. These findings suggest that increased AT2R expression may play a role in the observed decrease in inflammatory pathway activation through decreased TNF-α production and STAT3 signaling. Restoration of AT2R expression and/or its activation constitute a potentially novel therapeutic target for the management of inflammatory processes.

Original languageEnglish (US)
Pages (from-to)471-474
Number of pages4
JournalJournal of Interferon and Cytokine Research
Volume31
Issue number6
DOIs
StatePublished - Jun 1 2011

ASJC Scopus subject areas

  • Immunology
  • Cell Biology
  • Virology

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