ABSTRACT
Background The rejection following keratoplasty still is a leading cause of corneal transplantation failure.Studies showed that the interleukin-22 (IL-22) ,one of the effector molecules of T helper cell 17 (Th17) participated on the rejection after heart,liver and bone marrow transplantation.However,the effect of IL-22 on corneal graft rejection is not well understood.Objective This study was to investigate the expression of IL-22 mRNA in the corneal grafts and the role of IL-22 in the immune rejection after corneal transplantation in rats.Methods Seventy-two Wistar rats were randomized into autologous keratoplasty group,allograft keratoplasty group and anti-rejection group,and other 4 normal Wistar rats served as normal control group.Autologous keratoplasty was operated on the Wistar rats of the autologous keratoplasty group,and allograft keratoplasty were carried out with the 24 SD rats as donors and 48 Wistar rats as recipients.Tobramycin and dexamethasone eye drops were topically administrated after autologous keratoplasty for 2 weeks in the anti-rejection group.The experimental eyes were examined by slit lamp microscope after surgery and graft survival was evaluated based on the rejection scoring criteria of Larkin.Intergroup accumulated survival rates of grafts were compared using Kaplan-Meier analysis.Histopathological examination of grafts was carried out in 5 and 14 days after operation respectively,and the related expression levels of IL-22 mRNA and aryl hydrocar-bon receptor (AhR) mRNA were carried out by real-time fluorescence quantitative PCR.The feeding and use of the experimental animals followed the Guangdong provincial regulations on the management of experimental animals.The experimental design was approved by the ethics committee of Southern Medical University.Results The median survival time of grafts in the allograft keratoplasty group was 10 days,and that in the anti-rejection group was 17 days,showing a significant survival extention in the anti-rejection group (x2=16.442,P =0.000).Significant differences were found among the 4 groups in the related expression levels of IL-22 mRNA in both 5 days and 14 days after surgery (postoperative 5 days : F=2.44,P =0.00;postoperative 14 days: F=267.92, P =0.00), and the related expression levels of IL-22 mRNA were remarkably higher in the allograft keratoplasty group than those in the anti-rejection group at different time points (postoperative 5 days :9.70±0.35 vs.0.46±0.21;postoperative 14 days : 23.12 ± 1.89 vs.3.14±0.94) (both at P＜0.05).The related expression levels of AhR mRNA in the grafts were considerably different among the 4 groups (postoperative 5 days : F =395.73, P =0.00;postoperative 14 days : F =942.37, P =0.00) , and the expression levels were significantly elevated in the allograft keratoplasty group compared with the anti-rejection group at various time points (postoperative 5 days:2.52±0.32 vs.1.89±0.10;postoperative 14 days:7.20±0.25 vs.2.60±0.17) (both at P＜0.05).Conclusions The expression level of IL-22 RNA up-regulates in the grafts with immuno-rejection.Topical administration of tobramycin and dexamethasone eye drops inhibits the rejection after keratoplasty.AhR plays a regulative role to the expression of IL-22 in rats after keratoplasty.
ABSTRACT
Objective To investigate the expression of cellular chemokine CCL22 and its receptor CCR4, as well as its clinical significance in systemic lupus erythematosus (SLE), along with its roles in the pathogenesis of this disease. Methods Forty-eight patients with SLE and 26 normal human controls were recruited into this study. The patient cohort included 2 males and 46 females with an average age of 33.98± 12.73 years and disease course of 1 month to 20 years. Blood samples were collected from the subjects. ELISA and flow cytometry were used to examine the plasma concentration of CCL22 together with the CCR4 expression on peripheral blood cells. SLEDAI was applied to evaluate the severity of SLE patients. Results The plasma concentration of CCL22 was 227.03±122.84 ng/L in SLE group, 369.53±79.10 ng/L in the control group, 168.09±61.83 ng/L in patients with lupus nephritis and 292.77±163.45 ng/L in patients without lupus nephritis; there was a significant difference between the SLE patients and normal con-trols (P < 0.05) as well as between patients with lupus nephritis and those without (P < 0.05). Increased percentage of CCR4-expressing cells were observed in the peripheral blood of patients with SLE compared with the controls (20.24%±13.86% vs 10.44%±3.07%, P < 0.01), and the percentage of CD3+CCR4+ cells was significantly higher than that of CD3-CCR4+ cells. Moreover, a decrease was noted in the plasma con-centration of CCL22 in severe patients (P < 0.05). In SLE patients, the percentage of CCR4 increased with the rise in SLEDAI score, whereas the plasma concentration of CCL22 negatively correlated with SLEDAI score (r = -0.308, P < 0.05). Conclusion CCL22/CCR4 may play a certain role in the development, pro-gression and organ involvement in SLE.