C-X3-C motif chemokine ligand 1/receptor 1 regulates the M1 polarization and chemotaxis of macrophages after hypoxia/reoxygenation injury

Abstract Background Macrophages play an important role in renal ischemia reperfusion injury, but the functional changes of macrophages under hypoxia/reoxygenation and the related mechanism are unclear and need to be further clarified. Methods The effects of hypoxia/reoxygenation on functional characteristics of RAW264.7 macrophages were analyzed through the protein expression detection of pro-inflammatory factors TNF-α and CD80, anti-inflammatory factors ARG-1 and CD206. The functional implications of C-X3-C motif chemokine receptor 1(CX3CR1) down-regulation in hypoxic macrophages were explored using small interfering RNA technology. Significance was assessed by the parametric t-test or nonparametric Mann–Whitney test for two group comparisons, and a one-way ANOVA or the Kruskal–Wallis test for multiple group comparisons. Results Hypoxia/reoxygenation significantly increased the protein expression of M1-related pro-inflammatory factors TNF-α, CD80 and chemokine C-X3-C motif chemokine ligand 1 (CX3CL1)/CX3CR1 and inhibited the protein expression of M2-related anti-inflammatory factors ARG-1 and CD206 in a time-dependent manner in RAW264.7 cells. However, the silencing of CX3CR1 in RAW264.7 cells using specific CX3CR1-siRNA, significantly attenuated the increase in protein expression of TNF-α (P Conclusions The findings suggest that hypoxia/reoxygenation could promote M1 polarization, cell migration, and adhesion of macrophages, and that polarized macrophages induce further apoptosis of hypoxic renal tubular epithelial cells by regulating of CX3CL1/CX3CR1 signaling pathway.