title: Regulation of the macrophage oxytocin receptor in response to inflammation.
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/11signaling 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.
authors.affiliation: Department of Psychology, University of Miami, Coral Gables, Florida; and.
authors.forename: Angela
authors.initials: A
authors.lastname: Szeto
authors.affiliation: Department of Psychology, University of Miami, Coral Gables, Florida; and.
authors.forename: Ni
authors.initials: N
authors.lastname: Sun-Suslow
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism and Diabetes Research Institute, Miller School of Medicine, University of Miami, Florida.
authors.forename: Armando J
authors.initials: AJ
authors.lastname: Mendez
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism and Diabetes Research Institute, Miller School of Medicine, University of Miami, Florida.
authors.forename: Rosa I
authors.initials: RI
authors.lastname: Hernandez
authors.affiliation: Department of Psychology, University of Miami, Coral Gables, Florida; and.
authors.forename: Klaus V
authors.initials: KV
authors.lastname: Wagner
authors.affiliation: Department of Psychology, University of Miami, Coral Gables, Florida; and pmccabe@miami.edu.
authors.forename: Philip M
authors.initials: PM
authors.lastname: McCabe
mesh_terms: D000818:Animals; D015153:Blotting, Western; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D017737:Macrophages, Peritoneal; D008297:Male; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D010120:Oxytocics / Q000494:pharmacology; D010121:Oxytocin / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D016133:Polymerase Chain Reaction; D060888:Real-Time Polymerase Chain Reaction; D018045:Receptors, Oxytocin / Q000187:drug effects / Q000235:genetics*; D017483:Receptors, Vasopressin / Q000187:drug effects / Q000235:genetics
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010120:Oxytocics; D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin; D010121:Oxytocin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D043802:GTP-Binding Protein alpha Subunits, Gq-G11
keywords: acute-phase protein; inflammation; macrophages; oxytocin; oxytocin receptor