Glycyrrhizin and related compounds down-regulate production of inflammatory chemokines IL-8 and eotaxin 1 in a human lung fibroblast cell line.
Glycyrrhizin and related compounds down-regulate production of inflammatory chemokines IL-8 and eotaxin 1 in a human lung fibroblast cell line.
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DOI：
10.1016/j.intimp.2004.07.023
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发表时间：
2004-12-15
影响因子：
5.6
通讯作者：
Kasahara T
中科院分区：
文献类型：
--
作者：
Matsui S;Matsumoto H;Sonoda Y;Ando K;Aizu-Yokota E;Sato T;Kasahara T
甘草甜素（GL）具有多种免疫调节活性，长期以来在临床上用作抗过敏剂和抗肝炎剂。虽然GL对肺部炎性疾病的效力已被预期，但GL对肺部的影响仍知之甚少。肺成纤维细胞被认为是炎性趋化因子IL-8和嗜酸性粒细胞趋化因子1的有效产生者，在炎症期间，嗜中性粒细胞和嗜酸性粒细胞被其强烈吸引。因此，我们使用TNF-α和IL-4刺激的人胎肺成纤维细胞系HFL-1研究了GL对这些趋化因子产生的影响。此外，我们还研究了GL的构效关系，以探索更多有益的化合物。18α，β-GL呈剂量依赖性地抑制IL-8，轻微抑制eotaxin 1。18α，β-甘草次酸（GA）对IL-8无抑制作用，但对Eotaxin 1有抑制作用。18α，β-甘草次酸单葡萄糖醛酸苷（MGA）的作用与18α，β-GL相似，但较18α，β-GL弱。3β-[（2-O-β-d-吡喃葡萄糖醛酸基-β-d-吡喃葡萄糖醛酸基）氧基]-18β-11-脱氧-藜芦-12-烯-30-酸（11-deoxo-GL）和3β-[（2-O-β-d-吡喃葡萄糖醛酸基-β-d-吡喃葡萄糖醛酸基）氧基]-藜芦-11，13，（18）-二烯-30-酸（hetero-GL）均表现出抑制活性和显著的细胞毒性。3β-[（2-O-β-d-吡喃葡萄糖醛酸基-β-d-吡喃葡萄糖醛酸基）氧基]-18β-α-9，12-二烯-30-酸（homo-GL）无细胞毒性，但活性与18α，β-GL相似。3β-[（2-O-β-d-吡喃葡萄糖醛酸基-β-d-吡喃葡萄糖醛酸基）氧基]-藜芦-11，13（18）-二烯-30-醇（杂-30-OH-GL）和3β-[（2-O-β-d-吡喃葡萄糖醛酸基-β-d-吡喃葡萄糖醛酸基）氧基]-18β-藜芦-9，12-二烯-30-醇（高-30-OH-GL）在低于18α，β-GL的浓度下显示出强效抑制作用，且无显著细胞毒性。这些结果表明，GL相关化合物在减少趋化因子产生方面是有效的，并且鉴于其抑制能力和较小的细胞毒性，包括杂-30-OH-GL和均-30-OH-GL的GL修饰的化合物似乎最有益。
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.
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影响因子：
4.8
作者：
Kitaura, M;Nakajima, T;Yoshie, O
通讯作者：
Yoshie, O
影响因子：
4.4
作者：
Chibana, K;Ishii, Y;Fukuda, T
通讯作者：
Fukuda, T
影响因子：
15.9
作者：
Lilly, CM;Nakamura, H;Luster, AD
通讯作者：
Luster, AD
DOI：
10.1084/jem.167.6.1883
发表时间：
1988-06-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Matsushima K;Morishita K;Yoshimura T;Lavu S;Kobayashi Y;Lew W;Appella E;Kung HF;Leonard EJ;Oppenheim JJ
通讯作者：
Oppenheim JJ
影响因子：
3.8
作者：
Miyamasu, M;Nakajima, T;Hirai, K
通讯作者：
Hirai, K