All-Trans Retinoic Acid Attenuates Interleukin-23/Interleukin-17 Pathway and Promotes Skin Allograft Survival in Mice / 天津医药

ABSTRACT

Objective To investigate the effects of all-trans retinoic acid (ATRA)-intragastric-administration on the survival time of mouse skin allografts and the role of interleukin (IL)-23 and IL-17 thereof. Methods The skin trans-plantation of mice was done by DBA/2 as donors and Balb/c as recipients. The recipients were divided randomly into three groupscontrol group, low-dose group and high-dose group. Mice of the corresponding groups were intragastrically adminis-tered corn oil, 10 mg/kg ATRA and 30 mg/kg ATRA respectively from 1 day before the transplantation to the 14th day after the transplantation. The survival time of transplanted skin was observed after the operations. Skin grafts of mice were harvested for histopathological examination in three groups. The serum levels of IL-23 and IL-17 were measured by enzyme-linked im-munosorbent assay (ELISA). The expression levels of IL-23, RORγt and IL-17 mRNA in skin allografts were detected by re-al-time fluorescent quantitative reverse transcriptase polymerase chain reaction (RT-PCR). Results Compared with con-trol group, the average survival time of mouse skin allografts was significantly prolonged in low-dose group and high-dose group (P＜0.05). The less lymphocyte infiltration and destruction of architecture were found in the skin biopsies. The serum expression of IL-23 protein was lower (P＜0.05), but no significant difference was found in two treatment groups. The serum expression levels of IL-17 protein were reduced in turn in receptors of control group, low-dose group and high-dose group (P ＜ 0.05). The expression levels of IL-23, RORγt and IL-17 mRNA in skin grafts were significantly lower in low-dose group and high-dose group than those of control group (P＜0.05), but no significant difference was found in two treatment groups. Conclusion ATRA can effectively prolong the survival time of skin allografts, which may related with the inhibi-tion of the expression of IL-23, RORγt and IL-17 mRNA and the development of IL-23 and IL-17 protein.