Celastrol suppresses IFN-gamma-induced ICAM-1 expression and subsequent monocyte adhesiveness via the induction of heme oxygenase-1 in the HaCaT cells

被引：45

作者：

Seo, Won Yong ^{[1
,2
]}

Ju, Sung Mi ^{[1
,2
]}

Song, Ha Yong ^{[1
,2
]}

Goh, Ah Ra ^{[1
,2
]}

Jun, Jong-Gab ^{[3
]}

Kang, Young-Hee ^{[4
]}

Choi, Soo Young ^{[1
,2
]}

Park, Jinseu ^{[1
,2
]}

机构：

[1] Hallym Univ, Dept Biomed Sci, Chunchon 200702, Kangwon Do, South Korea

[2] Hallym Univ, Res Inst Biosci & Biotechnol, Chunchon 200702, Kangwon Do, South Korea

[3] Hallym Univ, Dept Chem, Chunchon 200702, Kangwon Do, South Korea

[4] Hallym Univ, Dept Food Sci & Nutr, Chunchon 200702, Kangwon Do, South Korea

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2010年 / 398卷 / 01期

关键词：

Celastrol; ICAM-1; HO-1; Inflammation; Keratinocyte; IFN-gamma; NF-KAPPA-B; ADHESION MOLECULES; HUMAN KERATINOCYTE; ENDOTHELIAL-CELLS; OXIDATIVE STRESS; INTERFERON-GAMMA; GOD VINE; ACTIVATION; ANTIOXIDANT; DISEASE;

D O I：

10.1016/j.bbrc.2010.06.053

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Celastrol, a quinone methide triterpenoid derived from the medicinal plant Tripterygium wilfordii, possesses various biological activities such as anti-oxidant, anti-tumor, and anti-inflammatory activities. In this study, we examined the suppressive effect of celastrol on IFN-gamma-induced expression of ICAM-1 and the molecular mechanism responsible for these activities. We found that celastrol induced mRNA and protein expression of heme oxygenase-1 (HO-1) in the human keratinocyte cell line HaCaT. Treatment of HaCaT cells with tin protoporphyrin IX (SnPP), a specific inhibitor of HO-1, reversed the suppressive effect of celastrol on IFN-gamma-induced protein and mRNA expression of ICAM-1. HO-1 knockdown using small interfering RNA (siRNA) led to reverse inhibition of IFN-gamma-induced up-regulation of ICAM-1 by celastrol. In addition, SnPP reversed suppression of IFN-gamma-induced promoter activity of ICAM-1 by celastrol. Furthermore, blockage of HO-1 activity by SnPP and HO-1 siRNA reversed the inhibitory effect of celastrol on IFN-gamma-induced adhesion of monocytes to keratinocytes. These results suggest that celastrol may exert anti-inflammatory responses by suppressing IFN-gamma-induced expression of ICAM-1 and subsequent monocyte adhesion via expression of HO-1 in the keratinocytes. (C) 2010 Elsevier Inc. All rights reserved.

引用

页码：140 / 145

页数：6

共 28 条

[1]

Heme oxygenase-1 mediates the anti-inflammatory actions of 2′-hydroxychalcone in RAW 264.7 murine macrophages [J].