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Vol. 58, Issue 3, 526-534, September 2000
B and Blocks Tumor
Necrosis Factor-
- 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
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-
,
interleukin-1, and bacterial lipopolysaccharide. The induction process
primarily takes place at the level of transcription, where nuclear
factor-
B (NF-B) 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- as determined by
reverse transcription-polymerase chain reaction, and therefore it may
interfere with the transcription of their genes. Because NF-B 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-B. These results
have implications for using NF-B inhibitors for the treatment of
various inflammatory diseases.
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