TNF-alpha upregulates VCAM-1 and NF-kappaB in fibroblasts from nasal polyps.

Abstract

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.

• Authors: Junichiro Ohori, Masato Ushikai, Dong Sun, Kengo Nishimoto, Yukari Sagara, Tatsuya Fukuiwa, Shoji Matsune, Yuichi Kurono
• Journal: Auris, nasus, larynx (Auris Nasus Larynx) Vol. 34 Issue 2 Pg. 177-83 (Jun 2007) ISSN: 0385-8146 [Print] Netherlands
• PMID: 16934424 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cysteine Proteinase Inhibitors
• Leupeptins
• NF-kappa B
• Tumor Necrosis Factor-alpha
• Vascular Cell Adhesion Molecule-1
• benzyloxycarbonylleucyl-leucyl-leucine aldehyde

Topics

• Cells, Cultured
• Cysteine Proteinase Inhibitors (pharmacology)
• Dose-Response Relationship, Drug
• Electrophoretic Mobility Shift Assay
• Enzyme-Linked Immunosorbent Assay
• Fibroblasts (pathology)
• Flow Cytometry
• Humans
• In Vitro Techniques
• Leupeptins (pharmacology)
• NF-kappa B (antagonists & inhibitors, metabolism)
• Nasal Polyps (pathology)
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Necrosis Factor-alpha (physiology)
• Up-Regulation (physiology)
• Vascular Cell Adhesion Molecule-1 (metabolism)