2′-Hydroxychalcone Inhibits Nuclear Factor-κB and Blocks Tumor Necrosis Factor-α- and Lipopolysaccharide-Induced Adhesion of Neutrophils to Human Umbilical Vein Endothelial Cells
- 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-α, interleukin-1, and bacterial lipopolysaccharide. The induction process primarily takes place at the level of transcription, where nuclear factor-κB (NF-κB) 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-α as determined by reverse transcription-polymerase chain reaction, and therefore it may interfere with the transcription of their genes. Because NF-κB 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-κB. These results have implications for using NF-κB inhibitors for the treatment of various inflammatory diseases.
Footnotes
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Send reprint requests to: Dr. B. Ghosh, Molecular Immunology and Immunogenetics Laboratory, Centre for Biochemical Technology, University of Delhi Campus (North), Mall Road, Delhi 110007, India. E-mail: bghosh{at}cbt.res.in
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↵1 Both authors contributed equally to this work.
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This work was supported by Council of Scientific and Industrial Research (CSIR), India, and Department of Biotechnology, India. B.M. is a recipient of CSIR fellowships.
- Abbreviations:
- ICAM-1
- intercellular adhesion molecule-1
- VCAM-1
- vascular cell adhesion molecule-1
- IL-1
- interleukin-1
- TNF-α
- tumor necrosis factor-α
- LPS
- lipopolysaccharide
- mAb
- monoclonal antibody
- NF-κB
- nuclear factor κB
- ELISA
- enzyme-linked immunosorbent assay
- HUVECs
- human umbilical vein endothelial cells
- RT-PCR
- reverse transcription-polymerase chain reaction
- DTT
- dithiothreitol
- EMSA
- electrophoretic mobility shift assay
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- Received January 10, 2000.
- Accepted June 6, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
