| Background:TNF-related apoptosis-inducing ligand (TRAIL) is a recently described member of the TNF superfamily. Death receptor 4 (DR4) is one of its receptor. DR4 contains death domains(DD) in its cytoplasmic region and can mediate cell apoptosis upon ligation with membrane from TRAIL.It has an important relationship between immune regulation and apoptosis induced by TRAIL. TRAIL participate in cytotoxic and(or) immune regulation which mediated by T-lymphocyte; and it is concerned with the development and differentation of immature dendritic cells (DC). Latest studies implicate that there may be a close relationship between TRAIL/DR4 and transplant immune rejection.The structures and functions of TRAIL are similar to FasL, they have the ability of inducing apoptosis in broad-spectrum. FasL is only expressed in activated T lymphocytes, NK cells and immune privilege organs(or tissues). TRAIL is widely expressed in a lot of tissues, especially in spleen, prostate and lung of adults. Research showed that the apoptosis mediated by Fas/FasL play an important role in corneal allograft immune; IL-1ra has an immunosuppressive effect and it can promote corneal allograft survival through Fas/FasL pathway . TRAIL and FasL are both the members of the TNF superfamily, the functions are resemblance between TRAIL andFasL. So we performed this experiment to investigate the expression of TRAIL and DR4 of cornea in situ in normal rats, and to study the expression of TRAIL and DR4 of the corneal ailografts during the acute immunological rejection in experimental penetrating keratoplasty in rats and to analysis the roles of TRAIL and DR4 in the corneal allograft rejection. Objective:1. To investigate the expression of TRAIL and DR4 of cornea in situ in normal rats.2. To study the expression of TRAIL and DR4 of the corneal ailografts during the acute immunological rejection in experimental penetrating keratoplasty in rats and to analysis the roles of TRAIL and DR4 in the corneal allograft rejection.3. To study the immunosuppressive effect of IL-lra and its effect on the expression of TRAIL and DR4 proteins on the corneal ailografts during the acute immunological rejection in experimental penetrating keratoplasty in rats.Methods:Corneal transplantation was performed orthotopically from Wistar rats to SD rats, recipients were randomly assigned to three groups: group I was treated by N.S; group II was treated by CsA; group HI was treated by IL-lra. Treatments were began on the first postoperative day. Mean survival times were determined. The eyes of six rats were enucleated randomly during the acute immunological rejection. The immunohistochemistry staining was adopted to examine the expression and distribution of TRAIL and DR4 proteins in corneal grafts during allograft rejection. At the same time, six corneas of normal Wistar rats were examined with above methods. Results:1. TRAIL and its receptor DR4 proteins were detected on normal cornea, they were mainly expressed on the epithelium and endothelium, with modest staining in thestroma.2. The expression of TRAIL and its receptor DR4 increased significantly during allograft rejection in the epithelium, endothelium and stroma of corneal allografts and the rate of acute rejection is 100 %.3. Mean survival time of transplants increased significantly in IL-Ira-treated group compared with other groups; the level of expressions of TRAIL and DR4 proteins in IL-Ira-treated group was markedly decreased in comparison with the N.S-treated group and CsA-treated group.Conclusions:1. The expression of TRAIL and DR4 proteins exist in normal cornea, they were mainly expressed on the epithelium.2. The expression of TRAIL and its receptor DR4 proteins increased during allograft rejection, they increased significantly on the epithelium, endothelium and stroma around the wound, they may invole in the acute immunological rejection in penetrating keratoplasty.3. Topical treatment with IL-lra has more significant positive effect in promoting corneal allograft survival through TRAH7DR4 pathway than CsA treatment.
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