Effects of interleukin (IL)-10/ transforming growth factor (TGF)-β-modified macrophages on renal ischemia reperfusion injury

Objective To investigate the effects of IL-10/TGF-β-modified macrophages on renal ischemia reperfusion injury (IRI). Methods Bone marrow-derived macrophages were modified ex vivo by IL-10/TGF-β to acquire M2c (a subset of activated macrophages). M2c were transferred into treated C57BL/6 mice by a single tail-vein injection at 6 h after renal IRI. Mice were killed on the day 3 after renal IRI. Blood samples were collected to check renal function. Kidneys were harvested to determine tubular necrosis and apoptosis by H&E staining and TUNEL assay. Immunofluorescence was performed to analyze the proliferating tubular cell nuclear antigen. Meanwhile, proinflammatory cytokines and regulatory T cells in renal tissues were analyzed with real-time PCR and flow cytometry. Results In comparison with M1, M2c expressed lower levels of MHC Ⅱ (P<0.01), CD86 (P<0.01), TNFα (P<0.01) and IL-1β (P<0.01) and higher level of IL-10 (P<0.01). M2c significantly attenuated renal functional decline (P<0.01 or 0.05), structural injury (P<0.05), apoptosis of tubular cells (P<0.01) and inflammation factors infiltration (P<0.01 or 0.05). What's more, the cells could promote tubular cells proliferation (P<0.05) and regulatory T cells expression (P<0.01). Conclusion Our results demonstrated that M2c macrophages effectively protect against renal IRI and may become a therapeutic strategy for renal IRI.