Effects of immunosuppressive agents on interleukin-2 and interleukin-2 receptor α mRNA expression

Abstract

IL-2 plays a central role in controlling the magnitude of immune response by interacting with its specific receptor (IL-2R) on cell surface. As the expressions of IL-2 and IL-2Rα, one of the three subunits of IL-2R, are controlled almost entirely at transcriptional level, any stimulus inhibiting IL-2 or IL-2Rα mRNA expression exerts profound effects on host immune system. In this study, the effects of various kinds of immunosuppressive agents on IL-2 and IL-2Rα mRNA expression were analyzed in mouse splenocytes using competitive RT-PCR method. The accuracy of this PCR-based analysis method, developed in this study, was verified by the linearity between the amounts of input template and that of the resulting PCR product. After activation with Con A (2㎍/ml), IL-2 mRNA levels peaked at 8 hr, while IL-2Rα mRNA transcripts increased gradually until 80 hr. Cyclosporin A, a well-known immunosuppressive drug, markedly inhibited IL-2Rα expression, as well as IL-2, at very low concentration (10 ng/ml). AAF and IQ also reduced the mRNA expression of both, IL-2 and IL-2Rα, to less than 30% of induced level. In the analysis of TCDD, no significant decrease in IL-2 mRNA transcript was detected. Among other chemicals (aflatoxin $B_1$, cyclophosphamide, DMBA) which need metabolic activation to exert their immunosuppressive effects, only DMBA showed inhibitory effects on IL-2 mRNA transcription after coculture with mouse hepatocytes.