Suppression of nuclear translocation of nuclear factor-kappaB and nuclear factor of activated T cells by Younggaechulgam-tang.
Younggaechulgam-tang (YGCGT) is known to suppress inflammatory and autoimmune responses, and it has clinically been used among Oriental medical doctors in South Korea. We investigated YGCGT-mediated changes in downstream T cell signal transduction. The expression levels of nuclear factor-kappaB (NFkappaB) subunit RelA and nuclear factor of activated T cells (NFATc1) in cytoplasm and nucleus were examined by western blot analysis. Interlukin-2 (IL-2) expression in MOLT-4 cells activated by phytohemagglutinin (PHA) was determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. IL-2 secretion was measured by an enzyme-linked immunosorbent assay (ELISA). PHA-induced translocation of Rel A and NFATcl to the nucleus were markedly reduced by YGCGT treatment. Furthermore, IL-2 mRNA and protein levels and IL-2 secretion were significantly diminished by YGCGT treatment. In conclusion, YGCGT treatment of T cells inhibits selectively nuclear translocation of RelA and NFATc1, resulting in diminished production of IL-2. These results suggest that YGCGT may have potential as immunosuppressive drugs with improved efficacy and reduced side effects.
Shin
Hye-Young
HY
Department of Pharmacology, College of Oriental Medicine, Kyung Hee University, Seoul, South Korea.
Song
Yung-sun
YS
Hwang
Chung-Yeon
CY
Shin
Tae-Yong
TY
Kim
Hyung-Min
HM
D021581:Active Transport, Cell Nucleus / Q000187:drug effects* / Q000276:immunology; D000076246:CCCTC-Binding Factor; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D007723:Korea; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008518:Medicine, East Asian Traditional; D016328:NF-kappa B / Q000276:immunology* / Q000378:metabolism; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins / Q000276:immunology* / Q000378:metabolism; D010835:Phytohemagglutinins / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D028321:Plant Preparations / Q000494:pharmacology; D021122:Protein Subunits; D012097:Repressor Proteins; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000276:immunology* / Q000378:metabolism
D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D004268:DNA-Binding Proteins; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D016328:NF-kappa B; D050778:NFATC Transcription Factors; C494003:NFATC1 protein, human; D009687:Nuclear Proteins; D010835:Phytohemagglutinins; D010936:Plant Extracts; D028321:Plant Preparations; D021122:Protein Subunits; D012097:Repressor Proteins; D014157:Transcription Factors; C500217:younggaechulgam-tang