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The function of the complement and macrophage crosstalk during the formation of crescents in lupus nephritis has not yet been reported. This study therefore aimed to explore the association of crescents, complements, and M2 macrophages with clinical features in lupus nephritis. We assessed a Chinese cohort comprising 301 patients with lupus nephritis. Renal biopsy specimens were collected from 64 patients with proliferative lupus nephritis (class III/III + V or IV/IV + V). The renal deposition of cluster of differentiation (CD) 68, inducible nitric oxide synthase, CD163, and C3a receptor (C3aR) was evaluated by immunostaining. The associations among crescents, complements, and M2 macrophages were also analyzed. Next, the underlying mechanism was investigated in vitro using C3a-treated macrophages. We found that M2-phenotype macrophages (CD163 + ) were the dominant subpopulation in human lupus nephritis. Additionally, a significant association was observed among the CD163 + macrophages, crescents, and complement activation. C3aR co-localized with CD163 and correlated with crescents and could induce polarization of macrophages to an M2 phenotype. Overall, these results suggest that complement-mediated M2/M1 macrophage polarization may contribute to the formation of crescents in lupus nephritis., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Calcineurin (CaN) plays an important role in glomerular hypertrophy and extracellular matrix accumulation in early diabetic nephropathy. Cyclosporine (CSA), a CaN inhibitor, has been shown to reduce renal injury in streptozotocin-induced diabetic rats. We examined whether FK506, which immunosuppressive action was 10-100 times of CSA, inhibits progression of diabetic nephropathy in experimental diabetic rats. Diabetes was induced with streptozotocin in rats, and FK506 (0.5 or 1.0mg/kg) was orally administered once a day for 4 weeks. Increased relative kidney weight was significantly reduced by FK506 treatment with 1.0mg/kg (p<0.05), and elevated 24 hour urinary albumin excretion rate was markedly attenuated by FK506 treatment with 0.5 and 1.0mg/kg (p<0.05, 0.01). Elevated glomerular volume was significantly attenuated by FK506 treatment with 0.5 and 1.0mg/kg (p<0.05), and increased indices for tubulointerstitial injury were only ameliorated by FK506 treatment with 1.0mg/kg (p<0.01). Western blot analysis noted that the expression of CaN protein was increased 2.4 fold in the kidney from diabetic rats, and FK506 treatment with 0.5 and 1.0mg/kg could reduce increased expression of CaN protein by 38.0% and 73.2%. The expression of 1α (IV) collagen, p65, p-p65, OPN, α-SMA and TGF-β1 protein in kidney was significantly increased in diabetic rats and reduced by FK506 treatment (p<0.05, 0.01). Our results show that FK506 could ameliorate renal injury in early experimental diabetic rats, which mechanism may be at least partly correlated with suppression on increased CaN in renal tissue in diabetic rats., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Baicalin (BA) exhibits anti-inflammatory effect in vivo and in vitro and is used to treat inflammatory diseases. Here, we report that BA inhibits the activation of macrophage and protects mice from macrophage-mediated endotoxin shock. The experiments in vitro showed BA suppressed the increased generation of nitric oxide (NO) and expression of inducible nitric oxide synthase (iNOS) induced by LPS or Interferon-gamma (IFN-gamma) without directly affecting iNOS activity in RAW264.7 cells and peritoneal macrophages. Similarly, BA inhibited the production of reactive oxidative species (ROS), whereas augmented the level of intracellular superoxide dismutase (SOD). Moreover, BA inhibited the production of inflammatory mediators including tumor necrosis factor (TNF)-alpha, endothelin (ET)-1 and thromboxane A2 (TXA2) induced by lipopolysaccharide (LPS) in RAW264.7 cells. In animal model, BA protected mice from endotoxin shock induced by d-galactosamine (D-GalN)/LPS possibly through inhibiting the production of cytokine and NO. Collectively, BA inhibited the production of inflammatory mediators by macrophage and may be a potential target for treatment of macrophage-mediated diseases.

Previously it was shown that treatment with mycophenolate mofetil (MMF) attenuated renal inflammation and glomerular injury in a model of diabetes. However, the mechanism involved in the renoprotective effects of MMF in experimental diabetes has not been clearly delineated. Diabetes was induced by injection of streptozotocin (STZ) after uninephrectomy. Diabetic animals received no treatment or treatment with MMF (10 mg/kg once daily by gastric gavage) for 8 weeks, non-diabetic rats served as controls. Level of malondialdehyde (MDA) in renal tissue and urine as well as the activity of antioxidant enzymes (AOE) in renal tissue was determined. Renal injury was evaluated. Immunohistochemistry for ED-1 macrophages marker, intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) was performed. Expression of transforming growth factor (TGF)-beta1 protein was determined by Western blotting analysis. Treatment with MMF had no effect on blood glucose level, but did prevent increased urinary albumin excretion and glomerular damage in diabetic rats. Oxidative stress was reduced by MMF treatment, as indicated by a reduction in MDA level in renal tissue and urine. Activity of AOE such as glutathione peroxidase (GSH-PX) was markedly elevated while superoxide dismutase (SOD) and catalase (CAT) were not changed by MMF treatment. In diabetic animals receiving no treatment, there were increases in ED-1-positive cells, ICAM-1 expression and MCP-1 expression in glomeruli and tubulointerstitium, which were effectively suppressed by MMF treatment. Western blotting analysis showed that the expression of TGF-beta1 protein was increased by 1.92-fold in renal tissue in diabetic rats, and MMF treatment significantly reduced the increased expression of TGF-beta1 protein by 45%. Our data suggest that MMF treatment ameliorates early renal injury via the inhibition of oxidative stress and overexpression of ICAM-1, MCP-1 and TGF-beta1 in renal tissue in diabetic rats.