Glycyrrhizin and related compounds down-regulate production of inflammatory chemokines IL-8 and eotaxin 1 in a human lung fibroblast cell line

Sachiko Matsui, Hiroatsu Matsumoto, Yoshiko Sonoda, Kumi Ando, Eriko Yokota, Toshitsugu Sato, Tadashi Kasahara

Research output: Contribution to journalArticle

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Abstract

Glycyrrhizin (GL) is known to have various immunomodulating activities and has long been used clinically as an anti-allergic and anti-hepatitis agent. While the potency of GL against lung inflammatory diseases has been expected, the effect of GL on the lung has been poorly understood. Lung fibroblasts are known as a potent producer of inflammatory chemokines, IL-8 and eotaxin 1, by which neutrophils and eosinophils are strongly attracted during inflammation. Therefore, we studied the effects of GL on the production of these chemokines using a human fetal lung fibroblast cell line, HFL-1, stimulated with TNF-α and IL-4. Moreover, we examined the structure-activity relationships of GL to explore more beneficial compounds. 18α,β-GL inhibited IL-8 dose-dependently and inhibited eotaxin 1 slightly. 18α,β-Glycyrrhetic acid (GA) did not inhibit IL-8 but inhibited eotaxin 1. The effect of 18α,β-glycyrrhetic acid monoglucuronide (MGA) resembled that of 18α,β-GL but was weaker. Both 3β-[(2-O-β-d- glucopyranuronosyl-β-d-glucopyranuronosyl)oxy]-18β-11-deoxo-olean-12- en-30-oic acid (11-deoxo-GL) and 3β-[(2-O-β-d-glucopyranuronosyl- β-d-glucopyranuronosyl)oxy]-olean-11,13,(18)-dien-30-oic acid (hetero-GL) exhibited inhibitory activity with significant cytotoxicity. 3β-[(2-O-β-d-Glucopyranuronosyl-β-d-glucopyranuronosyl)oxy] -18β-olean-9,12-dien-30-oic acid (homo-GL) did not have cytotoxicity but its activity was mild like that of 18α,β-GL. 3β-[(2-O-β-d- Glucopyranuronosyl-β-d-glucopyranuronosyl)oxy]-olean-11,13(18)-dien-30-ol (hetero-30-OH-GL) and 3β-[(2-O-β-d-glucopyranuronosyl-β-d- glucopyranuronosyl)oxy]-18β-olean-9,12-dien-30-ol (homo-30-OH-GL) showed potent inhibitory effects, at concentrations lower than 18α,β-GL with no significant cytotoxicity. These results suggest that GL-related compounds are effective in reducing chemokine production and that GL-modified compounds including hetero-30-OH-GL and homo-30-OH-GL appear most beneficial in view of their inhibitory capacity with less cytotoxicity.

Original languageEnglish
Pages (from-to)1633-1644
Number of pages12
JournalInternational Immunopharmacology
Volume4
Issue number13
DOIs
Publication statusPublished - 2004

Fingerprint

Chemokine CCL11
Glycyrrhizic Acid
Interleukin-8
Interleukin-1
Chemokines
Down-Regulation
Fibroblasts
Cell Line
Lung
Acids

Keywords

  • Eotaxin 1
  • Glycyrrhizin derivatives
  • Human lung fibroblast
  • IL-8

ASJC Scopus subject areas

  • Immunology
  • Pharmacology

Cite this

Glycyrrhizin and related compounds down-regulate production of inflammatory chemokines IL-8 and eotaxin 1 in a human lung fibroblast cell line. / Matsui, Sachiko; Matsumoto, Hiroatsu; Sonoda, Yoshiko; Ando, Kumi; Yokota, Eriko; Sato, Toshitsugu; Kasahara, Tadashi.

In: International Immunopharmacology, Vol. 4, No. 13, 2004, p. 1633-1644.

Research output: Contribution to journalArticle

Matsui, Sachiko ; Matsumoto, Hiroatsu ; Sonoda, Yoshiko ; Ando, Kumi ; Yokota, Eriko ; Sato, Toshitsugu ; Kasahara, Tadashi. / Glycyrrhizin and related compounds down-regulate production of inflammatory chemokines IL-8 and eotaxin 1 in a human lung fibroblast cell line. In: International Immunopharmacology. 2004 ; Vol. 4, No. 13. pp. 1633-1644.
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AU - Ando, Kumi

AU - Yokota, Eriko

AU - Sato, Toshitsugu

AU - Kasahara, Tadashi

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