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

Abstract

Background 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. Methods In 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. Results The 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. Conclusions This is the first study to demonstrate that macrophage polarization differentially regulates the expression of OT and OTR in enteric neurons.

Modulation of tumor‐associated macrophages in colitis‐associated colorectal cancer

“…OT signaling system are important pathways to prevent free radical damage cascade and alleviate colitis. In vitro, macrophages polarized into M1 type by LPS contained pro‐inflammatory cytokines (IL‐1β, IL‐6, and TNF‐α) in the supernatant of macrophages (Shi et al, 2021). Under the stimulation of IL‐4, MMs secretes anti‐inflammatory factors, which activate Smad2/3 pathway and upregulate OT signaling system by inhibiting the expression of PEG3 in intestinal neurons (Shi et al, 2021).…”

“…In vitro, macrophages polarized into M1 type by LPS contained pro‐inflammatory cytokines (IL‐1β, IL‐6, and TNF‐α) in the supernatant of macrophages (Shi et al, 2021). Under the stimulation of IL‐4, MMs secretes anti‐inflammatory factors, which activate Smad2/3 pathway and upregulate OT signaling system by inhibiting the expression of PEG3 in intestinal neurons (Shi et al, 2021). Thus, it can be concluded that the OT signaling system is likely to be the signaling molecule for the dialogue between intestinal macrophages and neurons, and the modulation of the MMs phenotype may be critical in determining homeostasis or disease propensity.…”

Muscularis Macrophages in Healthy and Diseased Gut

“…This has been shown in cell cultures of ENs, and the interaction is made possible via the STAT3 or NF-κΒ pathways. On the other side, anti-inflammatory MMs cause upregulation of oxytocin and its receptor via a TGF-β related mechanism [32]. Interestingly, lower concentrations of oxytocin and Muscularis Macrophages in Healthy and Diseased Gut DOI: http://dx.doi.org/10.5772/intechopen.109889 its receptor have been associated with more pro-inflammatory cytokines in mouse models of dextran sulfate sodium (DSS) associated colitis [33].…”

Neuroimmune regulation in Hirschsprung’s disease associated enterocolitis

“…In vitro , after macrophages were polarized to M1 type by LPS, pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) contained in macrophage supernatants inhibited the expression of OT and OTR in intestinal neurons; after macrophages were polarized to M2 type by IL4, anti-inflammatory cytokines (TGF-β) contained in macrophage supernatants promoted OT and OTR in intestinal neuronal expression. Therefore, it has been suggested that macrophages are polarized to M1 type during the inflammatory phase and to M2 type during the recovery process ( 84 ).…”