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

2010; Elsevier BV; Volume: 398; Issue: 1 Linguagem: Inglês

10.1016/j.bbrc.2010.06.053

1090-2104

Won Yong Seo, Sung Mi Ju, Ha Yong Song, Ah Ra Goh, Jong‐Gab Jun, Young‐Hee Kang, Soo Young Choi, Jinseu Park,

Natural Compounds in Disease Treatment

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-γ-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-γ-induced protein and mRNA expression of ICAM-1. HO-1 knockdown using small interfering RNA (siRNA) led to reverse inhibition of IFN-γ-induced up-regulation of ICAM-1 by celastrol. In addition, SnPP reversed suppression of IFN-γ-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-γ-induced adhesion of monocytes to keratinocytes. These results suggest that celastrol may exert anti-inflammatory responses by suppressing IFN-γ-induced expression of ICAM-1 and subsequent monocyte adhesion via expression of HO-1 in the keratinocytes.