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Objective To examine the inhibitory effect of IL-2-PE40 on the mouse corneal allograft rejection. Methods A mouse corneal graft model was set up by using C57BL/6 mice as donors and Balb/c mice as recipients. In the treatment group, IL-2-PE40 (0.6 μg/g body weight) was intraperitoneally injected from the day of surgery every 12 h until rejection happened. In the control group, the equal volume of PS was injected intraperitoneally at the corresponding time points. The transplanted cornea was observed under slit-lamp twice a week and the transplanted corneal opacity and neovascularization were rated according to Horis grading standards. It led to the determination of rejection response. The survival of transplanted cornea was regarded to be stopped when the rejection occurred. The operated eyes were observed historically on the 10th, 15th, 25th and 35th day after the surgery, and the peripheral blood was collected for measurement of T cell subgroups and T lymphocyte colonies. Results The survival time of cornea in the treatment and control groups was (30.2±2.9) days and (15.1±2.1) days respectively. In the control group, rejection occurred on the 15th day after the surgery, CD4~+ cells started rise right after the surgery and increased most obviously on the 15th day [(63.9±4.0)%] and decreased afterwards. CD4~+ cells in the treatment group were increased slightly [(42.6±4.0)%] on the 15th day. The number of CD4~+ cells in the treatment group was obviously less than in the control group (P<0.01). No significant changes in CD8~+ cells were observed in both groups. The number of T lymphocyte colonies in the control group was increased at the beginning and dropped then. No obvious change was found in the treatment group. The number of T lymphocyte colonies in the treatment group was significantly less than in the control group (P＜0.01). Conclusion IL-2-PE40 is a highly specific immunosuppressive agent. It can delay the development of corneal graft rejection and reduce the percentage of T-helper cells significantly. It also works to weaken the forming capacity of the peripheral T lymphocyte colonies.

9.Inhibitory effects of LY267108 on nuclear factor kappa B during osteoclast activation

Jian YU ; Jianning ZHAO

Chinese Journal of Tissue Engineering Research 2014;(15):2309-2313

BACKGROUND:No ideal drugs can be used in the prevention and treatment of aseptic loosening of artificial joints. Some researchs showed that erythromycin has strong inhibitory effects on periprosthetic osteolysis. Its antibacterial activity, however, limits its application in artificial joint loosening prevention. LY267108 is a new type of erythromycin derivatives, eliminates the antibacterial activities, and retains the anti-inflammatory activity.
OBJECTIVE:To evaluate inhibitory effect of LY267108 on nuclear factor kappa B during osteoclast activation.
METHODS:RANKL and macrophage colony-stimulating factor were added to RAW264.7 cellline of a mouse model induced by osteoclasts. Simultaneously, different concentrations of alendronate sodium, erythromycin and LY267108 were cocultured for 48 hours. The activity of nuclear factor kappa B and content of intracytoplasmic inhibitory subunit of nuclear factor kappa B alpha were measured by electrophoretic mobility shift assay and western blot assay.
RESULTS AND CONCLUSION:LY267108 has a strong inhibitory effect on nuclear factor kappa B. 10 mg/L LY267108, 25 mg/L erythromycin and 10 mg/L alendronate sodium had similar inhibitory effects on nuclear factor kappa B, which was obviously stronger than 10 mg/L erythromycin. However, 25 mg/L LY267108 had strongest inhibitory effects. No significant difference in intracytoplasmic inhibitory subunit of nuclear factor kappa B alpha levels was detected among 10 mg/L LY267108, 25 mg/L erythromycin and 10 mg/L alendronate sodium groups, but was stil apparently higher than 10 mg/L erythromycin group. Levels of intracytoplasmic inhibitory subunit of nuclear factor kappa B alpha were highest in the 25 mg/L LY267108 group. Results indicated that LY267108 in the process of osteoclast activation had stronger inhibitory effects on nuclear factor kappa B compared with erythromycin, and its safety was higher than alendronate sodium. Simultaneously, LY267108 did not have antimicrobial activity, and became a potential ideal drug for prevention and treatment of aseptic loosening of artificial joints. However, the inhibitory effects of LY267108 on the degradation of inhibitory subunit of nuclear factor kappa B alpha would be a mechanism of inhibiting the activation of nuclear factor kappa B.