The effect of macrophages polarization on the expression of oxytocin signaling system in enteric neurons

Abstract Background: The aim of the current study is to investigate the effect of macrophages polarization on the expression of oxytocin (OT) and oxytocin receptor (OTR) in enteric neurons. Methods: In this study, we used a classic colitis model to observe the correlation between macrophages polarization and OT signaling system. In order to further demonstrate the effect of macrophages, we examined the expression of OT signaling system after depletion of macrophages. Results: The data showed that, in vitro, flowing macrophages polarization to M1 type by LPS, the macrophages supernatant inhibited the expression of OT and OTR in cultured enteric neurons through releasing pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α); flowing macrophages polarization to M2 type by IL4, the macrophages supernatant promoted the expression of OT and OTR in cultured enteric neurons through releasing anti-inflammatory cytokine (TGF-β). Furthermore, M1 macrophages decreased the expression of OT signaling system mainly through STAT3/NF-κB pathways in cultured enteric neurons; M2 macrophages increased expression of OT signaling system mainly through activation of Smad2/3 and inhibiting the expression of Peg3 in cultured enteric neurons. In DSS model, we demonstrated that macrophages were polarized to M1 type during the inflammatory phases, the expression of OT and OTR decreased significantly; and macrophages were polarized to M2 type during the recovery phases, the expression of OT and OTR increased significantly. At the same time, we also found that D-mannose increased the expression of OT and OTR through polarization of macrophages to M2 type. Conclusions: This is the first time to prove that the polarization of macrophages differentially regulates the expression of OT and OTR in enteric neurons.