The immunosuppressive effect of Gamisanghyulyunbueum through inhibition of mitogen-activated protein kinase and nuclear factor activation in MOLT-4 cells.
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 NH2-terminal kinase is inhibited. In activated MOLT-4 cells, the nuclear localization of nuclear factor of activated T cells (NFATc) was blocked by GSHYBE (1 mg/ml). Also, degradation of inhibitor kappaB-alpha and transactivation by nuclear factor-kappaB (NF-kappaB)/Rel A were impaired by GSHYBE (1 mg/ml). Furthermore, interlukin (IL)-2, IL-4 and Interferen (IFN)-gamma secretion by PHA activated MOLT-4 cells and peripheral blood mononuclear cells (PBMC) were significantly diminishes following GSHYBE treatment (1 mg/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-kappaB, resulting in diminished secretion of IL-2.
Shin
Hye-Young
HY
College of Oriental Medicine, Kyung Hee University, Seoul, South Korea.
Jeong
Hyun-Ja
HJ
Na
Ho-Jeong
HJ
Kim
Hong-Joon
HJ
Moon
Goo
G
Shin
Tae-Yong
TY
Yang
Deok-Chun
DC
Hong
Seung-Heon
SH
Kim
Hyung-Min
HM
D000328:Adult; D001483:Base Sequence; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D016207:Cytokines / Q000378:metabolism*; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007124:Immunoenzyme Techniques; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D016207:Cytokines; D017931:DNA Primers; D004268:DNA-Binding Proteins; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; C504645:gamisanghyulyunbueum; D020928:Mitogen-Activated Protein Kinases