The immunosuppressive effect of Buchang-tang through inhibition of mitogen-activated protein kinase and nuclear factor activation in MOLT-4 cells.
Buchang-tang (BCT) has been known to suppress inflammatory and autoimmune responses. Accordingly, BCT has been clinically used in Korea as an immunomodulatory oriental medicine. Here, we report on the mechanism of action of BCT in activated MOLT-4 cells by determining the affected signaling pathways. BCT inhibits extracellular signal-regulated kinases (ERK)l/2 and p38 activation but does not interfere with phosphorylation of other mitogen-activated protein kinases, c-Jun NH2-terminal kinases 1/2 in MOLT-4 cells. The nuclear localization of nuclear factor of activated T cells 2 (NFATc) was blocked by BCT. Also, degradation of inhibitor kappaB-alpha and transactivation by nuclear factor-kappa B (NF-kappaB)/Rel A were impaired. Furthermore, interlukin (IL)-2 mRNA and protein levels were significantly diminished by BCT treatment. Our data indicate that BCT inhibits ERK1/2, p38 activation, nuclear translocation of NFATc, and NF-kappaB, resulting in diminished secretion of IL-2.
Shin
Hye-Young
HY
College of Oriental Medicine, Institute of Oriental Medicine, Kyung Hee University, 1 Hoegi-Dong, Dongdaemun-Gu, Seoul 130-701, South Korea.
Shin
Tae-Yong
TY
An
Nyeon-Hyoung
NH
Kim
Hyung-Ryong
HR
Chae
Han-Jung
HJ
Kim
Yun-Kyung
YK
Um
Jae-Young
JY
Hong
Seung-Heon
SH
Kim
Hyung-Min
HM
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D007723:Korea; D008519:Medicine, Traditional; D016328:NF-kappa B / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000037:antagonists & inhibitors*; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal; D051996:Transcription Factor RelA / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
D007166:Immunosuppressive Agents; D007376:Interleukin-2; D016328:NF-kappa B; D050778:NFATC Transcription Factors; C494003:NFATC1 protein, human; D010936:Plant Extracts; C498143:RELA protein, human; D051996:Transcription Factor RelA; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases