Key Event Overview
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AOPs Including This Key Event
|AOP Name||Event Type||Essentiality|
|The Adverse Outcome Pathway on binding of FK506-binding protein 12 (FKBP12) by calcineurin inhibitors leading to immunosuppression||KE||Strong|
Level of Biological Organization
How this Key Event works
FK506-FKBP complex interferes with NFAT nuclear localization to suppress the production of multiple classes of cytokines in T cells including L-2, which develops cytotoxic T cells as well as other actions. The suppressive effect of FK506 on mouse MLR, which has been thought to be the representative of IL-2 dependent T cell growth (Kino et al. 1987b). Main mode of actions for suppression of MLR with FK506 deems to result from the decreased production of cytokines including IL-2
How it is Measured or Detected
Suppression of cytotoxic T lymphocyte (CTL) activity can be measured by 51Cr release CTL assay. Suppression of MLR is also measurable by Incorporation of radioisotope (3H-thymidine).
Evidence Supporting Taxonomic Applicability
FK-506 suppresses production of IL-2, IL-3, and IFN-γ in mouse MLR (Kino et al. 1987b). It also suppresses production of cytotoxic T lymphocytes (CTL) (Kino et al. 1987a).In human MLR, as well, FK-506 has been reported to suppress IL-2 production and expression of IL-2 receptors (Kino et al. 1987a).
 Kino, T., Hatanaka, H., Miyata, S., Inamura, N., Nishiyama, M., Yajima, T., Goto, T., Okuhara, M., Kohsaka, M. and Aoki, H. (1987a). FK-506, a novel immunosuppressant isolated from a Streptomyces. II. Immunosuppressive effect of FK-506 in vitro. Journal of antibiotics. 40(9): 1256-1265.
 Kino, T., Hatanaka, H., Hashimoto, M., Nishiyama, M., Goto, T., Okuhara, M., Kohsaka, M., Aoki, H. and Imanaka, H. (1987b). FK-506, a novel immunosuppressant isolated from a Streptomyces. I. Fermentation, isolation, and physico-chemical and biological characteristics. Journal of antibiotics. 40(9): 1249-1255.