Search

Inflammation is involved in the development and/or progression of diabetic nephropathy (DN). Curcumin has been reported for its anti-inflammation activity in DN. However, the mechanisms involved in the renoprotective effects of curcumin have not been clearly demonstrated. In this study, we hypothesized that curcumin affected high glucose (HG)-induced inflammation profiles in vivo and in vitro and then prevented renal injury in diabetic rats via reversing cav-1 Tyr 14 phosphorylation that influenced TLR4 activation. Streptozotocin (STZ)-induced diabetic rats received vehicle or curcumin for twelve weeks and podocytes were treated with HG in the presence or absence of curcumin in vitro. To further evaluate the effect of cav-1 phosphorylation at Tyr 14 on HG-induced podocyte inflammation response and TLR4 activation, a recombinant plasmid GFP-Cav-1 Y14F with a mutated phosphorylation site of cav-1, was transfected into cultured podocytes. In vivo, curcumin improved histological abnormalities and fibrosis of a diabetic kidney, inhibited renal inflammatory gene expression and reduced cav-1 phosphorylation at Tyr 14 and the expression of TLR4. Pretreatment of podocytes with curcumin reduced HG-stimulated production of proinflammatory cytokines, TLR4 and the phosphorylation of cav-1. But immunohistochemistry in rat kidney showed that the elevation of TLR4 expression is more evident in the renal interstitum than in the glomerulus where podocytes are located, and the possibility that the anti-inflammatory effects of curcumin on other cells in the kidney may be mediated through the same molecular pathways as in podocytes. Our study suggests that curcumin treatment ameliorates DN via inhibition of inflammatory gene expression by reversing caveolin-1 Tyr 14 phosphorylation that influenced TLR4 activation. [ABSTRACT FROM AUTHOR]

Abstract: The effects of BCG heat shock protein 70 (BCG HSP70) gene transfection on tumorigenicity and immunogenicity of murine lymphocytic leukemia cell line (L1210) were studied. After HSP70 gene transfection, the tumor cells became strongly immunogenic and lost their tumorigenicity in syngeneic mice. It mainly exhibited that tumor growth was slow or without the formation of tumor, mean survival time of mice was significantly prolonged and a marked stimulating effect on L1210 specific Th1 cells detected by IFN-γ ELISPOT assay. Tumor-bearing mice treated with the L1210-HSP70 cells showed thorough coagulation necrosis and abundant CD8+ T lymphocyte infiltration. Meanwhile, as the tumor vaccine, the HSP70-transfected tumor cells could induce a protective immune response in vivo. It showed that the tumor growth was significantly inhibited, tumor diameter was markedly reduced and the survival time of tumor-bearing mice was further prolonged. Immunization with it also resulted in regression of the established L1210 tumor and prolonged survival time of mice. These results suggest that gene transfection of BCG HSP70 could effectively improve the immunogenicity of tumor cells and it may be used as a suitable candidate gene-modified cell vaccine for cancer immunotherapy. [Copyright &y& Elsevier]