title: 2'-hydroxychalcone inhibits nuclear factor-kappaB and blocks tumor necrosis factor-alpha- and lipopolysaccharide-induced adhesion of neutrophils to human umbilical vein endothelial cells.
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.
authors.affiliation: Molecular Immunology and Immunogenetics Laboratory, Centre for Biochemical Technology, University of Delhi Campus (North), Delhi, India.
authors.forename: B
authors.initials: B
authors.lastname: Madan
authors.forename: S
authors.initials: S
authors.lastname: Batra
authors.forename: B
authors.initials: B
authors.lastname: Ghosh
mesh_terms: D001692:Biological Transport; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D047188:Chalcones; D004305:Dose-Response Relationship, Drug; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D047188:Chalcones; D019040:E-Selectin; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D002599:Chalcone; C013031:2'-hydroxychalcone