Fig. 1.
MLN4924 significantly attenuated SLE progress of MRL/lpr mice. a The female MRL/lpr and MRL/MpJ mice (12 weeks) were randomly allocated into two groups and treated with either control or MLN4924 (10 mg/kg) following the indicated scheme. n = 5 (MRL/MpJ group) or n = 10 (MRL/lpr group). b The inhibition of neddylation with MLN4924 was evaluated via the neddylation level of Cullin1 in splenocytes. c Survival curve of MRL/lpr mice treated with control or MLN4924. n = 10 mice/group. *P < 0.05. d, e Spleen index (spleen weight /body weight ratio) and the number of splenocytes were calculated. n = 5 (MRL/MpJ group), 4 (MRL/lpr treated with DMSO), or 9 (MRL/lpr treated with MLN4924). *P < 0.05, **P < 0.01, ***P < 0.001. f, g The serum was collected at 20 weeks, followed by monitoring of IgG and anti-dsDNA antibody levels. n = 5 (MRL/MpJ group), 4 (MRL/lpr administered with DMSO), or 9 (MRL/lpr administered with MLN4924). *P < 0.05, **P < 0.01. h, i Total protein, albumin and creatinine in urine were assessed and albumin/creatinine was calculated. n = 5 (MRL/MpJ group), 4 (MRL/lpr administered with DMSO), or 9 (MRL/lpr administered with MLN4924). *P < 0.05, **P < 0.01. j Representative images of PAS staining of kidneys from 20-week-old mice. Scale bar = 50 µm. Then, pathological score was calculated. n = 5 (MRL/MpJ group), 4 (MRL/lpr administered with DMSO), or 9 (MRL/lpr administered with MLN4924). **P < 0.01, ***P < 0.001. k Cytokine profile in serum was analyzed using Bio-Plex ProTM Mouse Cytokine Th17 panel A6-plex. n = 5 (MRL/MpJ groups, MRL/lpr administered with MLN4924 group) or 4 (MRL/lpr administered with DMSO). *P < 0.05, **P < 0.01, ***P < 0.001