The Immunosuppressive Effect of Gamisanghyulyunbueum through Inhibition of Mitogen-Activated Protein Kinase and Nuclear Factor Activation in MOLT-4 Cells(Pharmacology)

概要

論文の詳細を見る
Gamisanghyulyunbueum (GSHYBE) has been used clinically to treat skin related disease in South Korea. We investigated GSHYBE-mediated changes in downstream T cell signal transduction. To determine the mechanism of inhibition, we have studied many of the major pathways in phytohemagglutinin (PHA)-activated T cell. We show that among the mitogen-activated protein kinase family activation of phosphorylation of extra cellular signal-regulated kinase 1/2 (ERK1/2, p44/42) and p38, but not c-jun NH_2-terminal kinase is inhibited. In activated MOLT-4 cells, the nuclear localization of nuclear factor of activated T cells (NFATc) was blocked by GSHYBE (1mg/ml). Also, degradation of inhibitor κB-α and transactivation by nuclear factor-κB (NF-κB)/Rel A were impaired by GSHYBE (1mg/ml). Furthermore, interlukin (IL)-2, IL-4 and Interferen (IFN)-γ secretion by PHA activated MOLT-4 cells and peripheral blood mononuclear cells (PBMC) were significantly diminishes following GSHYBE treatment (1mg/ml). Also, oral administration of GSHYBE inhibited IL-2 secretion in skin allergic reaction. In conclusion, our data indicate that GSHYBE treatment of T cells inhibits ERK1/2 and p38 activation and nuclear translocation of NFATc, NF-κB, resulting in diminished secretion of IL-2.
社団法人日本薬学会の論文
2005-07-01