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Department of Marine Molecular Biotechnology, College of Life Science, Gangneung-Wonju National UniversityAbstract Recently, we reported that diarylheptanoid hirsutenone (HST) effectively inactivated T lymphocytes. However,it has not been evaluated whether HST is involved in calcineurin or calmodulin inactivation. In the present study, cellswere treated with T-cell inhibitors with or without HST. Our results revealed that HST successfully inhibited expressionof T-helper type I (Th1) and Th2 cytokines. Co-treatment with HST and nuclear factor-activated T cell (NFAT) activationinhibitor III (INCA-6) showed a more sensitive effect than that with other inhibitors, suggesting that HST contributes toinhibition of dephosphorylation of NFAT in the cytosol. HST up-regulated cell cycle arrest genes and inhibited the growthof Staphylococcus aureus. These effects were confirmed in an NFAT electrophoretic-mobility shift assay via successfulinhibition of NFAT translocation and in the histological recovery in a 2,4-dinitrochloro benzene-induced in vivo model.Taken together, HST was shown to effectively inhibit T-cell activation via inhibition of cytosolic NFAT dephosphorylation,similar to INCA-6.Keywords: diarylheptanoid hirsutenone, calcineurin, calmodulin, T lymphocyte, nuclear factor-activated T cell

T-lymphocyte Inactivation and Anti-atopic Effects of Diarylheptanoid Hirsutenone Isolated from Alnus japonica