BACKGROUND: Epithelial cells and fibroblasts play an important role in allergic inflammation. Modulation of surface expression of adhesion molecules on epithelial cells by antiallergic drugs has been shown by both in vivo and in vitro studies. OBJECTIVE: The aim of the study was to evaluate the effect exerted by terfenadine and fexofenadine on adhesion molecules expression (CD54/ICAM-1 and CD29) of a human continuously cultured conjunctival epithelial cell line (WK) and a fibroblast cell line (HEL). METHODS: By means of flow cytometry analysis, we evaluated ICAM-1 and CD29 expression by WK and HEL epithelial cells in basal condition (at baseline) or after IFN gamma or TNF alpha stimulation in the presence or in the absence of terfenadine and fexofenadine. We also performed immunoenzymatic assays in order to evaluate soluble ICAM-1 released by WK cells and procollagen type I and III and IL6 released by HEL cells. RESULTS: Terfenadine and fexofenadine significantly reduced ICAM-1 basal expression on WK cells at the concentration of 1 microg/mL and 50 microg/mL, respectively. In addition, both terfenadine and fexofenadine were able to decrease soluble ICAM-1 levels in IFN gamma-stimulated WK cells. On HEL fibroblasts, fexofenadine only was able to inhibit ICAM-1 upregulation induced by IFN gamma. Concerning the release of fibroblast products, we observed a dose-dependent decrease of spontaneous IL6 release only in the presence of fexofenadine. CONCLUSION: This study shows that terfenadine and fexofenadine exert a biologic effect directly on epithelial cells and fibroblasts reducing ICAM-1 expression and partially reducing soluble ICAM-1 release.
BACKGROUND: Epithelial cells and fibroblasts play an important role in allergic inflammation. Modulation of surface expression of adhesion molecules on epithelial cells by antiallergic drugs has been shown by both in vivo and in vitro studies. OBJECTIVE: The aim of the study was to evaluate the effect exerted by terfenadine and fexofenadine on adhesion molecules expression (CD54/ICAM-1 and CD29) of a human continuously cultured conjunctival epithelial cell line (WK) and a fibroblast cell line (HEL). METHODS: By means of flow cytometry analysis, we evaluated ICAM-1 and CD29 expression by WK and HEL epithelial cells in basal condition (at baseline) or after IFN gamma or TNF alpha stimulation in the presence or in the absence of terfenadine and fexofenadine. We also performed immunoenzymatic assays in order to evaluate soluble ICAM-1 released by WK cells and procollagen type I and III and IL6 released by HEL cells. RESULTS:Terfenadine and fexofenadine significantly reduced ICAM-1 basal expression on WK cells at the concentration of 1 microg/mL and 50 microg/mL, respectively. In addition, both terfenadine and fexofenadine were able to decrease soluble ICAM-1 levels in IFN gamma-stimulated WK cells. On HEL fibroblasts, fexofenadine only was able to inhibit ICAM-1 upregulation induced by IFN gamma. Concerning the release of fibroblast products, we observed a dose-dependent decrease of spontaneous IL6 release only in the presence of fexofenadine. CONCLUSION: This study shows that terfenadine and fexofenadine exert a biologic effect directly on epithelial cells and fibroblasts reducing ICAM-1 expression and partially reducing soluble ICAM-1 release.
Authors: G M Walsh; L Annunziato; N Frossard; K Knol; S Levander; J M Nicolas; M Taglialatela; M D Tharp; J P Tillement; H Timmerman Journal: Drugs Date: 2001 Impact factor: 9.546