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Biochem Biophys Res Commun. 2010 Jul 16;398(1):140-5. doi: 10.1016/j.bbrc.2010.06.053. Epub 2010 Jun 17.

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

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1
Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.

Abstract

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.

PMID:
20599745
DOI:
10.1016/j.bbrc.2010.06.053
[Indexed for MEDLINE]

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