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/G 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.

Oxytocin receptor agonist reduces perinatal brain damage by targeting microglia

“…The blockage of carbetocin effect by OXTR antagonist L‐368,899 further confirmed the functional expression OXTR on primary cultured microglia. Indeed, the biological action of OTX is linked to the activation of OXTR, a selective seven‐transmembrane G q / G i ‐coupled receptor expressed both in astrocytes and in microglia (Karelina et al, ; Yuan et al, ), particularly in response to inflammation (Szeto et al, ). Indeed, exposure of microglial cells to inflammatory stimulus induced a time‐dependent increase in OTXR expression suggesting that the sensitivity of microglia to OTX could be potentiated in response to an immune challenge.…”

“…The blockage of carbetocin effect by OXTR antagonist L-368,899 further confirmed the functional expression OXTR on primary cultured microglia. Indeed, the biological action of OTX is linked to the activation of OXTR, a selective seven-transmembrane G q /G i -coupled receptor expressed both in astrocytes and in microglia (Karelina et al, 2011;Yuan et al, 2016), particularly in response to inflammation (Szeto et al, 2017).…”

Chronic Hypopituitarism Associated with Increased Postconcussive Symptoms Is Prevalent after Blast-Induced Mild Traumatic Brain Injury

“…Deficiencies in oxytocin appear to be associated with psychiatric conditions involving deficits in social behavior including autism spectrum disorders and schizophrenia ( 84 – 86 ). Although findings in the literature lack consistency, recent research on both central and peripheral actions of oxytocin have identified potential relationships with mood and anxiety ( 87 ), learning and memory ( 88 ), improvement of wound healing ( 89 ), modulation of inflammatory responses ( 90 , 91 ), neuroprotection ( 89 , 91 , 92 ), regulation of food intake and body weight ( 93 ), and reduction of pain sensitivity ( 94 , 95 ).…”

Role of oxytocin in the control of stress and food intake

“…In laboratory animals and humans, oxytocin has been reported to reduce activity of the hypothalamic-pituitary adrenal axis, [38][39][40][41][42] attenuate inflammation 43,44 and reduce anxiety-related behaviours. In laboratory animals and humans, oxytocin has been reported to reduce activity of the hypothalamic-pituitary adrenal axis, [38][39][40][41][42] attenuate inflammation 43,44 and reduce anxiety-related behaviours.…”

“…Oxytocin has been shown to modulate stress responses in the neuroendocrine system, autonomic nervous system and immune system and in behaviours. In laboratory animals and humans, oxytocin has been reported to reduce activity of the hypothalamic-pituitary adrenal axis, [38][39][40][41][42] attenuate inflammation 43,44 and reduce anxiety-related behaviours. 7,39,[45][46][47][48] Oxytocin-deficient female mice have been shown to exhibit enhanced corticosterone release in response to shaker stress, enhanced novel environment-induced hyperthermia and increased anxiety-related behaviours in an elevated plus maze test.…”