| RRC ID |
42541
|
| 著者 |
Matsui S, Sonoda Y, Sekiya T, Aizu-Yokota E, Kasahara T.
|
| タイトル |
Glycyrrhizin derivative inhibits eotaxin 1 production via STAT6 in human lung fibroblasts.
|
| ジャーナル |
Int Immunopharmacol
|
| Abstract |
We recently demonstrated that glycyrrhizin (GL) and its derivatives down-regulate TNFalpha- 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 (3beta-[(2-O-beta-D-glucopyranuronosyl-beta-D-glucopyranuronosyl)oxy]-olean-11,13(18)-dien-30-ol) showed marked inhibition of eotaxin 1 production with less cytotoxicity than 18beta-GL. To identify the molecular mechanism of this effect, we focused on the inhibition of the transcriptional factors NF-kappaB 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 18beta-GL and significantly inhibited by hetero-30-OH-GL. While IkappaBalpha degradation and translocation of NF-kappaB 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.
|
| 巻・号 |
6(3)
|
| ページ |
369-75
|
| 公開日 |
2006-3-1
|
| DOI |
10.1016/j.intimp.2005.08.025
|
| PII |
S1567-5769(05)00251-1
|
| PMID |
16428072
|
| MeSH |
Cells, Cultured
Chemokine CCL11 / biosynthesis*
Chemokine CCL11 / genetics
Electrophoretic Mobility Shift Assay
Fibroblasts / drug effects*
Glycyrrhizic Acid / analogs & derivatives*
Glycyrrhizic Acid / pharmacology*
Humans
Lung / cytology*
Lung / drug effects
NF-kappa B / metabolism
Promoter Regions, Genetic
RNA Stability
RNA, Messenger / metabolism
STAT6 Transcription Factor / physiology*
|
| IF |
3.943
|
| 引用数 |
21
|
|
WOS 分野
|
PHARMACOLOGY & PHARMACY
IMMUNOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
HFL-I(RCB0521) |
