In Vitro Study Of FK506and FK1706in Immunosuppression And Axonal Regeneration

Background and objective:Tacrolimus (FK506) is widely used in organ transplantation. However, it also hasneurotrophic activity that occurs independently of its immunosuppressive effects.FK1706, a derivative of FK506, is a non-immunosuppressive immunophilin ligandwith significant neurotrophic activity. But its immunosuppressive effect and the effectof nerve regeneration are not yet clear. Here, we tested the different effect of FK506and FK1706on immunosuppression in peripheral blood mononuclear cells and nerveregeneration in SH-SY5Y.Methods:1. Different dose of FK506and FK1706intervention in peripheral bloodmononuclear cells, divided into nine groups: control group, different dose of FK506group (0.1nM,1nM,10nM,100nM), different dose of FK1706group (0.1nM,1nM,10nM,100nM), cell proliferation evaluated by MTT while IL-2levels in PBMCevaluated by ELISA.2. Different dose of FK506and FK1706intervention SH-SH5Y cells, dividedinto nine groups: sham group, different concentrations of FK506group (0.1nM,1nM,10nM,100nM), different concentrations of FK1706group (0.1nM,1nM,10nM,100nM). The number of cells, changes in synaptic cell body diameter and the axonallength was observed by the inverted microscope. Results:1. FK506at the dose of10nM and100nM induced cell death in PBMCs. Thedose of0.1nM and1nM reduced the cell proliferation and IL-2secretion inconcentration-and time-dependent manners (p<0.05).2. FK1706induced the decrease of in PBMC proliferation and IL-2secretion.Compared to the control group,0.1nM was not statistically significant,1nM,10nM,100nM showed concentration-and time-dependent manners(p<0.05), but theimmunosuppression compared to the same dose of FK506was significantlyattenuated(p<0.05).3. Compare to the sham group, both FK506and FK1706could effectivelypromote neurite outgrowth in SH-SY5Y cells (p<0.05), there was no significantdifference between the two drugs (p>0.05).Conclusion:FK506can promote axonal regeneration but inhibit the PBMC proliferation andIL-2secretion. Compare to FK506, FK1706decrease immunosuppression whilepromote nerve regeneration, which may be a beneficial strategy for nerve injury.