Quercetin Inhibits Lipopolysaccharide-lnduced Expression of Endothelial Cell Intracellular Adhesion Molecule-1

Quercetin Adhesion Inflammation Lymphocyte Endothelium Correspondence to: Dr. Elliott Middleton, Jr., MD, State University of New York at Buffalo, Allergy/Immunology Division, Buffalo General Hospital, 100 High Street, Buffalo, NY 14203 (USA) Introduction Adhesion molecules are essentially involved in the patho genesis of inflammation. Their presence and activity on vascular endothelial and circulating leukocytes is required to initiate and perpetuate an inflammatory process. Down-regulation of an inflammatory response can be achieved by limiting the expression or function of appropriate endothelial cell or leukocyte adhesion molecules. Quercetin is a common, naturally occurring, low-molecular-weight dietary plant flavonoid, structurally related to the antiallergic drugs cromolyn and nedocromil. It can inhibit tetradecanoylphorbol acetate-induced mononuclear cell aggregation [1] as well as cytotoxic lymphocyte (CTL) generation in murine mixed lymphocyte culture [2]. In addition, the cytotoxic activity of the CTL against P815 mastocytoma target cells is also inhibited. Each of these quercetin-sensitive processes is adhesion molecule dependent. Materials and Methods We investigated the effect of quercetin on (1) the attachment of peripheral blood lymphocytes (PBLs) to lipopolysaccharide (LPS)stimulated human umbilical vein endothelial cells (HUVECs) utilizing 5lCr-labelled PBLs, and (2) the attachment of a fluorescein-la-belled monoclonal antibody against intercellular adhesion molecule-1 (ICAM-1) on LPS-stimulated HUVECs. Results The results showed that quercetin (1) inhibited the attachment of labelled PBLs to LPSstimulated HUVECs but did not affect the control level of attachment of PBLs to HUVECs, and (2) inhibited the expression of ICAM-1 on the surface of LPS-stimulated HUVEC. In both processes, the quercetin effect was concentration dependent (IC50= 4μg/ml, 1-3 μM). Taxifolin (dihydroquercetin) had a negligible effect, indicating important structure-activity rela-