Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
Biochem Biophys Res Commun. 2010 Jul 16;398(1):140-5. doi: 10.1016/j.bbrc.2010.06.053. Epub 2010 Jun 17.
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.
雷公藤红素是从药用植物雷公藤中提取的一种醌甲基三萜，具有抗氧化、抗肿瘤和抗炎等多种生物活性。本研究探讨了雷公藤红素对 IFN-γ诱导的 ICAM-1 表达的抑制作用及其作用机制。结果发现，雷公藤红素诱导人角质形成细胞系 HaCaT 中血红素加氧酶-1（HO-1）的 mRNA 和蛋白表达。HO-1 的特异性抑制剂锡原卟啉 IX（SnPP）处理 HaCaT 细胞可逆转雷公藤红素对 IFN-γ诱导的 ICAM-1 蛋白和 mRNA 表达的抑制作用。用小干扰 RNA（siRNA）敲低 HO-1 可逆转雷公藤红素对 IFN-γ诱导的 ICAM-1 上调的抑制作用。此外，SnPP 逆转了雷公藤红素对 IFN-γ诱导的 ICAM-1 启动子活性的抑制作用。此外，SnPP 和 HO-1 siRNA 阻断 HO-1 活性可逆转雷公藤红素对 IFN-γ诱导的单核细胞与角质形成细胞黏附的抑制作用。这些结果表明，雷公藤红素可能通过在角质形成细胞中表达 HO-1 来抑制 IFN-γ诱导的 ICAM-1 表达及其随后的单核细胞黏附，从而发挥抗炎作用。
