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

Seo WY; Ju SM; Song HY; Goh AR; Jun JG; Kang YH; Choi SY; Park J

doi:10.1016/j.bbrc.2010.06.053

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

Seo WY ¹,

Ju SM ,

Song HY ,

Goh AR ,

Jun JG ,

Kang YH ,

Choi SY ,

Park J

Affiliations

1. Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
Authors
Seo WY¹
(1 author)

Biochemical and Biophysical Research Communications, 17 Jun 2010, 398(1):140-145
https://doi.org/10.1016/j.bbrc.2010.06.053 PMID: 20599745

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.

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References

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Funding

Funders who supported this work.

Korean Government (MEST)

Ministry of Education, Science and Technology (1)

Grant ID: 2009-0093812
4 publications

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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.

Affiliations

Authors

Abstract

Full text links

References

Marked synergism between tumor necrosis factor-alpha and interferon-gamma in regulation of keratinocyte-derived adhesion molecules and chemotactic factors.

Tumor necrosis factor beta and ultraviolet radiation are potent regulators of human keratinocyte ICAM-1 expression.

Adhesion of T lymphoblasts to epidermal keratinocytes is regulated by interferon gamma and is mediated by intercellular adhesion molecule 1 (ICAM-1).

Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications.

Heme oxygenase-1 inhibits T cell-dependent skin inflammation and differentiation and function of antigen-presenting cells.

Heme oxygenase 1 attenuates the development of atopic dermatitis-like lesions in mice: implications for human disease.

Heme oxygenase-1 attenuates contact hypersensitivity induced by 2,4-dinitrofluorobenzene in mice.

Celastrol, a potent antioxidant and anti-inflammatory drug, as a possible treatment for Alzheimer's disease.

The triterpene celastrol as a very potent inhibitor of lipid peroxidation in mitochondria.

Celastrol, a triterpene extracted from the Chinese "Thunder of God Vine," is a potent proteasome inhibitor and suppresses human prostate cancer growth in nude mice.

Citations & impact

Impact metrics

Citations of article over time

Smart citations by scite.ai
Explore citation contexts and check if this article has been supported or disputed.
https://scite.ai/reports/10.1016/j.bbrc.2010.06.053

Article citations

GRAS-microparticle microarrays identify dendritic cell tolerogenic marker-inducing formulations.

Celastrol Modulates Multiple Signaling Pathways to Inhibit Proliferation of Pancreatic Cancer via DDIT3 and ATF3 Up-Regulation and RRM2 and MCM4 Down-Regulation.

Tripterygium hypoglaucum (Lévl.) Hutch and Its Main Bioactive Components: Recent Advances in Pharmacological Activity, Pharmacokinetics and Potential Toxicity.

Butyrate Decreases ICAM-1 Expression in Human Oral Squamous Cell Carcinoma Cells.

Antitumor activity of celastrol by inhibition of proliferation, invasion, and migration in cholangiocarcinoma via PTEN/PI3K/Akt pathway.

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Funding

Korean Government (MEST)

Ministry of Education, Science and Technology (1)

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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.

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Ministry of Education, Science and Technology (1)﻿

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Ministry of Education, Science and Technology (1)