The effect of macrophage polarization on the expression of the oxytocin signalling system in enteric neurons

Yao Shi,Chuanyong Liu,Jianchun Zhu,Haojie Zhang,Bing Yan,Jingxin Li,Shuang Li,Tongtong Che

doi:10.1186/s12974-021-02313-w

Abstract

BackgroundThe aim of the current study was to investigate the effect of macrophage polarization on the expression of oxytocin (OT) and the oxytocin receptor (OTR) in enteric neurons.MethodsIn this study, we used a classic colitis model and D-mannose model to observe the correlation between macrophage polarization and OT signalling system. In order to further demonstrate the effect of macrophages, we examined the expression of OT signalling system after depletion of macrophages.ResultsThe data showed that, in vitro, following polarization of macrophages to the M1 type by LPS, the macrophage supernatant contained proinflammatory cytokines (IL-1β, IL-6 and TNF-α) that inhibited the expression of OT and OTR in cultured enteric neurons; following macrophage polarization to the M2 type by IL4, the macrophage supernatant contained anti-inflammatory cytokines (TGF-β) that promoted the expression of OT and OTR in cultured enteric neurons. Furthermore, M1 macrophages decreased the expression of the OT signalling system mainly through STAT3/NF-κB pathways in cultured enteric neurons; M2 macrophages increased the expression of the OT signalling system mainly through activation of Smad2/3 and inhibition of the expression of Peg3 in cultured enteric neurons. In a colitis model, we demonstrated that macrophages were polarized to the M1 type during the inflammatory phase, with significant decreased in the expression of OT and OTR. When macrophages were polarized to the M2 type during the recovery phase, OT and OTR expression increased significantly. In addition, we found that D-mannose increased the expression of OT and OTR through polarization of macrophages to the M2 type.ConclusionsThis is the first study to demonstrate that macrophage polarization differentially regulates the expression of OT and OTR in enteric neurons.

Highlights

Oxytocin (OT) is traditionally considered a nonapeptide hormone synthesized in the hypothalamus that is released from the posterior pituitary into circulation [1, 2] and is involved in milk let-down and uterine contraction [3]
Effect of macrophage polarization on the OT signalling system To investigate the effect of macrophage polarization on the OT signalling system, we determined the position of OT in enteric neurons and further confirmed that OT was expressed in the bodies and nerve fibres
Our current study demonstrates that macrophage polarization affects the expression of the OT signalling system in the gut

Summary

Introduction

Oxytocin (OT) is traditionally considered a nonapeptide hormone synthesized in the hypothalamus that is released from the posterior pituitary into circulation [1, 2] and is involved in milk let-down and uterine contraction [3]. Recent studies have shown that the oxytocin receptor (OTR) is widely present in the central and peripheral systems [3,4,5]. Studies in our laboratory and others have made clear that OT is an endogenous neuropeptide in the gastrointestinal tract and regulates the secretion, motility, and immunity of the digestive tract [9,10,11]. OT is mainly expressed in the myenteric nerve plexus and submucosal nerve plexus, including neuron bodies and nerve fibres [12]. The aim of the current study was to investigate the effect of macrophage polarization on the expression of oxytocin (OT) and the oxytocin receptor (OTR) in enteric neurons

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