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TNF-alpha upregulates VCAM-1 and NF-kappaB in fibroblasts from nasal polyps
Junichiro Ohori1, Masato Ushikai, Dong Sun
1Department of Otolaryngology, Field of Sensory Organology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima 890-8520, Japan. juno@m3.kufm.kagoshima-u.ac.jp
Objective:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
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