T-lymphocyte Inactivation and Anti-atopic Effects of Diarylheptanoid Hirsutenone Isolated from Alnus japonica
2013
Lee, D.I., Chung-Ang University, Republic of Korea | Seo, S.J., Chung-Ang University, Republic of Korea | Joo, S.S., Gangneung-Wonju National University, Republic of korea
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, cells were treated with T-cell inhibitors with or without HST. Our results revealed that HST successfully inhibited expression of T-helper type I (Th1) and Th2 cytokines. Co-treatment with HST and nuclear factor-activated T cell (NFAT) activation inhibitor III (INCA-6) showed a more sensitive effect than that with other inhibitors, suggesting that HST contributes to inhibition of dephosphorylation of NFAT in the cytosol. HST up-regulated cell cycle arrest genes and inhibited the growth of Staphylococcus aureus. These effects were confirmed in an NFAT electrophoretic-mobility shift assay via successful inhibition 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.
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