Regulation of the macrophage oxytocin receptor in response to inflammation

Angela Szeto, Ni Sun-Suslow, Armando J Mendez, Rosa I. Hernandez, Klaus V. Wagner, Philip McCabe

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

It has been demonstrated that the neuropeptide oxytocin (OT) attenuates oxidative stress and inflammation in macrophages. In the current study, we examined the role of inflammation on the expression of the oxytocin receptor (OXTR). We hypothesized that OXTR expression is increased during the inflammation through a nuclear factor-κB (NF-κB)-mediated pathway, thus responding as an acute-phase protein. Inflammation was induced by treating macrophages (human primary, THP-1, and murine) with lipopolysaccharide (LPS) and monitored by expression of IL-6. Expression of OXTR and vasopressin receptors was assessed by qPCR, and OXTR expression was confirmed by immunoblotting. Inflammation upregulated OXTR transcription 10- to 250-fold relative to control in THP-1 and human primary macrophages and increased OXTR protein expression. In contrast, vasopressin receptor-2 mRNA expression was reduced following LPS treatment. Blocking NF-κB activation prevented the increase in OXTR transcription. OT treatment of control cells and LPS-treated cells increased ERK1/2 phosphorylation, demonstrating activation of the OXTR/Gαq/11 signaling pathway. OT activation of OXTR reduced secretion of IL-6 in LPS-activated macrophages. Collectively, these findings suggest that OXTR is an acute-phase protein and that its increased expression is regulated by NF-κB and functions to attenuate cellular inflammatory responses in macrophages.

Original languageEnglish (US)
Pages (from-to)E183-E189
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume312
Issue number3
DOIs
StatePublished - 2017

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Keywords

  • Acute-phase protein
  • Inflammation
  • Macrophages
  • Oxytocin
  • Oxytocin receptor

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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