leupeptins and Nasal-Polyps

Lung and synovial fibroblasts produce VCAM-1 in response to TNF-alpha. However, the massive infiltration of eosinophils, the effects of the increased amount of TNF-alpha and the production of VCAM-1 in human nasal polyp fibroblasts are not yet fully understood. The present study examines the role of VCAM-1 and the molecular mechanism of its expression in nasal fibroblasts.. Nasal fibroblasts were isolated from human nasal polyps and after four passages, the cells were stimulated with TNF-alpha and VCAM-1 expression was examined by ELISA, flow cytometry, and RT-PCR. The activation of NF-kappaB induced by TNF-alpha was determined by electrophoretic mobility shift assays and the influence on the expression of VCAM-1 was investigated.. VCAM-1 protein and mRNA were expressed in unstimulated controls and remarkably increased by TNF-alpha stimulation. NF-kappaB activity was enhanced by TNF-alpha stimulation and remarkably suppressed by NF-kappaB proteasome inhibitor.. The present study discovered that nasal fibroblasts produce VCAM-1 protein and mRNA and that production is increased by TNF-alpha stimulation. Furthermore, VCAM-1 expression in nasal fibroblasts is induced through an NF-kappaB-dependent pathway. These findings might provide a rationale for using NF-kappaB inhibitors as a treatment for nasal inflammatory diseases such as polyps.

Topics: Cells, Cultured; Cysteine Proteinase Inhibitors; Dose-Response Relationship, Drug; Electrophoretic Mobility Shift Assay; Enzyme-Linked Immunosorbent Assay; Fibroblasts; Flow Cytometry; Humans; In Vitro Techniques; Leupeptins; Nasal Polyps; NF-kappa B; Reverse Transcriptase Polymerase Chain Reaction; Tumor Necrosis Factor-alpha; Up-Regulation; Vascular Cell Adhesion Molecule-1