Abstract
We recently demonstrated that glycyrrhizin (GL) and its derivatives down-regulate TNFα- and IL-4-induced eotaxin 1 production by the human fetal lung fibroblast line HFL-1 at protein or mRNA levels. In particular, the GL derivative hetero-30-OH-GL (3β-[(2-O-β-d-glucopyranuronosyl-β- d-glucopyranuronosyl)oxy]-olean-11,13(18)-dien-30-ol) showed marked inhibition of eotaxin 1 production with less cytotoxicity than 18β-GL. To identify the molecular mechanism of this effect, we focused on the inhibition of the transcriptional factors NF-κB and signal transducer and activator of transcription 6 (STAT6), which regulate eotaxin 1 gene activation. STAT6 phosphorylation and translocation of phospho-STAT6 from cytosol to nuclei were slightly inhibited by 18β-GL and significantly inhibited by hetero-30-OH-GL. While IκBα degradation and translocation of NF-κB p65 to nuclei were not significantly affected by either compound, the stability of eotaxin-1 mRNA was decreased with hetero-30-OH-GL. In addition, eotaxin 1 promoter activity was markedly inhibited by hetero-30-OH-GL. Electrophoretic mobility shift assay (EMSA) confirmed these results. Thus, hetero-30-OH-GL significantly inhibited eotaxin 1 expression by the selective inhibition of IL-4 signal transduction as well as by enhanced mRNA degradation.
| Original language | English |
|---|---|
| Pages (from-to) | 369-375 |
| Number of pages | 7 |
| Journal | International Immunopharmacology |
| Volume | 6 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2006 Mar |
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Keywords
- Eotaxin 1
- Glycyrrhizin derivatives
- Human lung fibroblast
- Nuclear factor-kappa B
- Signal transducer and activator of transcription 6
ASJC Scopus subject areas
- Immunology
- Pharmacology
Cite this
Glycyrrhizin derivative inhibits eotaxin 1 production via STAT6 in human lung fibroblasts. / Matsui, Sachiko; Sonoda, Yoshiko; Sekiya, Takashi; Yokota, Eriko; Kasahara, Tadashi.
In: International Immunopharmacology, Vol. 6, No. 3, 03.2006, p. 369-375.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Glycyrrhizin derivative inhibits eotaxin 1 production via STAT6 in human lung fibroblasts
AU - Matsui, Sachiko
AU - Sonoda, Yoshiko
AU - Sekiya, Takashi
AU - Yokota, Eriko
AU - Kasahara, Tadashi
PY - 2006/3
Y1 - 2006/3
N2 - We recently demonstrated that glycyrrhizin (GL) and its derivatives down-regulate TNFα- and IL-4-induced eotaxin 1 production by the human fetal lung fibroblast line HFL-1 at protein or mRNA levels. In particular, the GL derivative hetero-30-OH-GL (3β-[(2-O-β-d-glucopyranuronosyl-β- d-glucopyranuronosyl)oxy]-olean-11,13(18)-dien-30-ol) showed marked inhibition of eotaxin 1 production with less cytotoxicity than 18β-GL. To identify the molecular mechanism of this effect, we focused on the inhibition of the transcriptional factors NF-κB and signal transducer and activator of transcription 6 (STAT6), which regulate eotaxin 1 gene activation. STAT6 phosphorylation and translocation of phospho-STAT6 from cytosol to nuclei were slightly inhibited by 18β-GL and significantly inhibited by hetero-30-OH-GL. While IκBα degradation and translocation of NF-κB p65 to nuclei were not significantly affected by either compound, the stability of eotaxin-1 mRNA was decreased with hetero-30-OH-GL. In addition, eotaxin 1 promoter activity was markedly inhibited by hetero-30-OH-GL. Electrophoretic mobility shift assay (EMSA) confirmed these results. Thus, hetero-30-OH-GL significantly inhibited eotaxin 1 expression by the selective inhibition of IL-4 signal transduction as well as by enhanced mRNA degradation.
AB - We recently demonstrated that glycyrrhizin (GL) and its derivatives down-regulate TNFα- and IL-4-induced eotaxin 1 production by the human fetal lung fibroblast line HFL-1 at protein or mRNA levels. In particular, the GL derivative hetero-30-OH-GL (3β-[(2-O-β-d-glucopyranuronosyl-β- d-glucopyranuronosyl)oxy]-olean-11,13(18)-dien-30-ol) showed marked inhibition of eotaxin 1 production with less cytotoxicity than 18β-GL. To identify the molecular mechanism of this effect, we focused on the inhibition of the transcriptional factors NF-κB and signal transducer and activator of transcription 6 (STAT6), which regulate eotaxin 1 gene activation. STAT6 phosphorylation and translocation of phospho-STAT6 from cytosol to nuclei were slightly inhibited by 18β-GL and significantly inhibited by hetero-30-OH-GL. While IκBα degradation and translocation of NF-κB p65 to nuclei were not significantly affected by either compound, the stability of eotaxin-1 mRNA was decreased with hetero-30-OH-GL. In addition, eotaxin 1 promoter activity was markedly inhibited by hetero-30-OH-GL. Electrophoretic mobility shift assay (EMSA) confirmed these results. Thus, hetero-30-OH-GL significantly inhibited eotaxin 1 expression by the selective inhibition of IL-4 signal transduction as well as by enhanced mRNA degradation.
KW - Eotaxin 1
KW - Glycyrrhizin derivatives
KW - Human lung fibroblast
KW - Nuclear factor-kappa B
KW - Signal transducer and activator of transcription 6
UR - http://www.scopus.com/inward/record.url?scp=31044450232&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=31044450232&partnerID=8YFLogxK
U2 - 10.1016/j.intimp.2005.08.025
DO - 10.1016/j.intimp.2005.08.025
M3 - Article
VL - 6
SP - 369
EP - 375
JO - International Immunopharmacology
JF - International Immunopharmacology
SN - 1567-5769
IS - 3
ER -