-Melanocyte Stimulating Hormone (MSH) decreases cyclosporine A induced apoptosis in cultured human proximal tubular cells

The pathogenesis of chronic cyclosporine A (CsA) nephrotoxicity has not been elucidated, but apoptosis is thought to play an important role in CsA induced tubular atrophy. Recently Fas-Fas ligand system mediated apoptosis has been frequently reported in many epithelial cells as well as in T lymphocytes. We investigated the ability of CsA to induce apoptosis in cultured human proximal tubular epithelial cells and also the effect of -MSH on them. Fas, Fas ligand, and an intracellular adaptor protein, Fas-associating protein with death domain (FADD) expression, and poly-ADP ribose polymerase (PARP) cleavage were also studied. CsA induced apoptosis in cultured tubular epithelial cells demonstrated by increased number of TUNEL positive cells and it was accompanied by a significant increase in Fas mRNA and Fas ligand protein expressions. FADD and the cleavage product of PARP also increased, indicating the activation of caspase. In -MSH co-treated cells, apoptosis markedly decreased with downregulation of Fas, Fas ligand and FADD expressions and also the cleavage product of PARP. In conclusion, these data suggest that tubular cell apoptosis mediated by Fas system may play a role in tubular atrophy in chronic CsA nephrotoxicity and pretreatment of -MSH may have a some inhibitory effect on CsA induced tubular cell apoptosis.

Influence of anti-tumor drugs on immune escape and counterattack of colon cancer cells / 中国药理学通报

AIM Fas system plays an important role in the mechanism of immune escape and counterattack of colon cancer cells. This study was to investigate the influence of anti-tumor drugs on Fas, Fas ligand expressions on colon cancer cells. METHODS MTT method was used to get the inhibition concentration 50%(IC_ 50 ) of 5-fluorouracil (5-Fu), mitomycin (MMC), cisplatin (CP) to SW480. The concentrations of anti-tumor drugs were 0, 0.5 IC_ 50 , IC_ 50 , 2 IC_ 50 , respectively. Immmunocytochemical staining and flow cytometry analysis were used to detect the expression rates of Fas and FasL on SW480 cells before and after 5-Fu, MMC, CP treatments. In situ hybridyzation was used to observe Fas, FasL mRNA in SW480 cells before and after treatments. RESULTS IC_ 50 of 5-Fu, MMC, CP to SW480 were 11.70, 3.12, 3.40 mg?L -1 , respectively. Both immmunocytochemical staining and flow cytometry analysis found that without drug treatments SW480 expressed high FasL and low Fas, after the treatment of 5-Fu, Fas expression rates on SW480 increased but FasL remained unchanged; both Fas and FasL increased after the treatment of MMC or CP. In situ hybridization showed that after the treatment of 5-Fu and Fas mRNA on SW480 increased while FasL mRNA remained unchanged; both Fas mRNA and FasL increased after the treatment of MMC or CP. CONCLUSION Anti-tumor drugs can change the expression of Fas system on SW480 cells in different ways. MMC and CP can increase the sensitivity of colon cancer cells to apoptosis signals; at the same time, they possibly facilitate immune escape of tumor cells. However, 5-Fu does not have influence on immune escape of colon cancer cells. The target point is at the level of transcription or above it.-