The role of MIF-dependent macrophages in cisplatin induced acute kidney injury

Objective To investigate the role and mechanism of macrophage migration inhibitor (MIF)-dependent macrophages in cisplatin-induced acute kidney injury （AKI）. Methods MIF gene knockout male mice were randomly divided into the normal control group （n = 6） and experimental group （n = 18）. Mice in the normal control group were injected with saline via the tail vein. In the experimental group, the AKI mouse models were established by intraperitoneal injection of cisplatin. At 6 h after AKI model establishment, the mice were randomly divided into the AKI model group, macrophage control group, and MIF^-/- macrophage group （n = 6 in each group）, which were injected with saline, macrophages from C57BL/6J mice and macrophages from MIF^-/- mice through the tail vein, respectively. After 3-d feeding, the blood and renal tissue samples were collected. The renal function, pathological changes of renal tissues, the localization and expression of monocyte chemoattractant protein-1 （MCP-1） and tumor necrosis factor-α （TNF-α） were evaluated. The expression levels of Mincle, inducible nitric oxide synthase （iNOS） and F4/80 proteins in the kidney were quantitatively detected. Results Compared with the AKI model group, the serum level of creatinine was significantly up-regulated （P < 0.001）, the renal tubular necrosis was significantly aggravated （P < 0.001）, the expression levels of MCP-1 and TNF-α proteins in the kidney were remarkably up-regulated （both P < 0.01), and the ratio of M1 macrophages was significantly increased （P < 0.001） in the macrophage control group. Compared with the macrophage control group, the serum level of creatinine was significantly down-regulated （P < 0.001）, the renal tubular necrosis was considerably alleviated （P < 0.001）, the expression levels of MCP-1and TNF-α proteins in the kidney were remarkably down-regulated （both P < 0.01）, and the ratio of M1 macrophages was significantly decreased （P < 0.001） in the MIF^-/- macrophage group. Conclusion During the process of cisplatin-induced AKI, MIF promotes the activation of macrophages and increases the production of inflammatory cytokines by activating Mincle, which exacerbates the renal inflammatory injury.