The effects of TYB-2285 and its metabolites on eosinophil adhesion to tumor necrosis factor α-stimulated human umbilical vein endothelial cells

Abstract

The effects of TYB-2285 and its metabolites (TC-286 and TC- 326) on the adhesion of eosinophils and neutrophils to cultured human umbilical vein endothelial cells (HUVEC) stimulated with tumour necrosis factor α (TNF-α) were investigated. The treatment of HUVEC with TNF-α enhanced eosinophil adhesion in a dose-dependent manner (1–100 U/mL). The adhesion of eosinophils to TNF-α (100U/mL)-stimulated HUVEC was inhibited by TYB-2285 and its metabolites in a dose-dependent manner (10−8–10−5mol/L). These compounds showed stronger inhibitory effects than any other anti-allergic drugs, such as disodium cromoglycat (DSCG), ketotifen and tranilast. TYB-2285, TC-286 and TC-326 did not inhibit the adhesion of neutrophils at the same range (10−8–l 0−5 mol/L). In our adhesion assay system, eosinophil adhesion to TNF-α-stimulated HUVEC was blocked by monoclonal antibody against VLA-4 (anti-VLA-4) but not by that against Mac-1 (anti-Mac-1). In contrast, neutrophil adhesion was blocked by anti-Mac-1, but not by anti-VLA-4. The results of the present study demonstrate that TYB-2285 and its metabolites selectively inhibit the adhesion of eosinophils to HUVECs stimulated with TNF-α and also suggest that TYB-2285, TC-286 and TC-326 might block the VLA-4/VCAM-1 pathway selectively.

Keywords

• adhesion
• eosinophils
• TNF-α
• TYB-2285
• VLA-4