title: [A mechanism for the anti-inflammatory effect of nedocromil; inhibition of both adhesion molecule expression on eosinophils and endothelial cells, and eosinophil chemotactic activities].
abstract: The accumulation of eosinophils in the airway is one of the characteristics seen in patients with bronchial asthma. One of the newly developed anti-asthma drugs (controller), nedocromil sodium (nedocromil) is known to suppress the influx of eosinophils into allergic lesions. However, little is known about this mechanism. Therefore, in this report we investigated the effects of nedocromil on Mac-1 expression on PAF-stimulated eosinophils, and adhesion molecule expression on endothelial cells stimulated by either IL-1 beta or IL-4. We also investigated the eosinophil chemotaxis. A significant suppression of the Mac-1 expression on PAF-induced eosinophils was observed at both concentrations of 10(-5) and 10(-7) M of nedocromil. The expression of adhesion molecules, particularly ICAM-1 and E-selectin, on IL-1 beta-stimulated human umbilical vascular endothelial cells (HUVEC) was significantly suppressed at these concentrations, whereas the VCAM-1 expression was not changed. No significant suppression of VCAM-1 expression on IL-4-stimulated HUVEC was observed, although there was a tendency of suppression at these concentrations. On the other hand, the expression of the E-selectin molecule was significantly suppressed by nedocromil even under resting (non-stimulated) condition. PAF-induced eosinophil chemotactic activities were also suppressed at these concentrations in a dose-dependent manner. These results suggested that nedocromil suppressed the influx of eosinophils to inflammatory lesions by inhibiting not only the expression of the Mac-1 on eosinophils and of E-selectin and ICAM-1 molecules on HUVEC, but also the eosinophil chemotactic activities.
authors.affiliation: Dept. of Pulmonary Medicine and Clinical Immunology, Dokkyo University School of Medicine.
authors.forename: T
authors.initials: T
authors.lastname: Okada
authors.forename: H
authors.initials: H
authors.lastname: Sagara
authors.forename: Y
authors.initials: Y
authors.lastname: Nakano
authors.forename: T
authors.initials: T
authors.lastname: Hiyama
authors.forename: T
authors.initials: T
authors.lastname: Fukuda
mesh_terms: D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004727:Endothelium / Q000166:cytology; D004804:Eosinophils / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis*; D016177:Macrophage-1 Antigen / Q000032:analysis*; D017835:Nedocromil / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis*
chemical_list: D018927:Anti-Asthmatic Agents; D016177:Macrophage-1 Antigen; D019010:Vascular Cell Adhesion Molecule-1; D017835:Nedocromil; D018799:Intercellular Adhesion Molecule-1