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Mol Pharmacol. 2000 Sep;58(3):526-34.

2'-hydroxychalcone inhibits nuclear factor-kappaB and blocks tumor necrosis factor-alpha- and lipopolysaccharide-induced adhesion of neutrophils to human umbilical vein endothelial cells.

Author information

1
Molecular Immunology and Immunogenetics Laboratory, Centre for Biochemical Technology, University of Delhi Campus (North), Delhi, India.

Abstract

Inhibition of expression of cell adhesion molecules (CAM), including intercellular CAM-1 (ICAM-1), vascular CAM-1 (VCAM-1), and E-selectin, has been shown to be important in controlling various inflammatory diseases. The cell adhesion proteins are induced by various inflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-1, and bacterial lipopolysaccharide. The induction process primarily takes place at the level of transcription, where nuclear factor-kappaB (NF-kappaB) plays a major role. We demonstrate here that 2'-hydroxychalcone inhibits the adhesion of peripheral neutrophils to the endothelial cell monolayers by inhibiting the expression of ICAM-1, VCAM-1, and E-selectin in a concentration-dependent manner. The inhibition by 2'-hydroxychalcone is reversible. 2'-hydroxychalcone inhibits the induction of steady-state transcript levels of ICAM-1, VCAM-1, and E-selectin by tumor necrosis factor-alpha as determined by reverse transcription-polymerase chain reaction, and therefore it may interfere with the transcription of their genes. Because NF-kappaB is a major transcription factor involved in CAM expression, we studied its status in the 2'-hydroxychalcone treated cells. We demonstrate that 2'-hydroxychalcone inhibits the activation of NF-kappaB. These results have implications for using NF-kappaB inhibitors for the treatment of various inflammatory diseases.

PMID:
10953045
DOI:
10.1124/mol.58.3.526
[Indexed for MEDLINE]

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