C-C chemokine ligand 2 gene expression in nasal polyp fibroblasts: possible implication in the pathogenesis of nasal polyposis.

Abstract

OBJECTIVES:

Recruitment of macrophages is essential to the pathogenesis of nasal polyps (NP), since this disease is inflammation-related. In this study, the effects of tumor necrosis factor alpha (TNF-alpha) on the expression of C-C chemokine ligand 2 (CCL2) in fibroblasts derived from nasal polyps (NPFs) were investigated. The roles of cyclooxygenase (COX) 2 and prostaglandins in the mediation of TNF-alpha-stimulated CCL2 gene expression were also investigated.

METHODS:

Northern blot analysis was used to study the expression of CCL2 and c-Fos in cultured NPFs. An electrophoretic mobility shift assay was used to explore the interactions between activator protein 1 (AP- 1) and DNA. Immunohistochemistry was used to explore the in vivo expressions of COX-2, CCL2, and CD68 in NPs.

RESULTS:

The Northern blot analysis showed that TNF-alpha stimulated the expression of CCL2 and COX-2 genes, and the synthesis of CCL2 messenger RNA was COX-2-dependent. A transient elevation of c-Fos and c-Jun messenger RNAs was induced by TNF-alpha, whereas COX-2 inhibitors NS-398 and meloxicam abolished the up-regulation of c-Fos. The electrophoretic mobility shift assay revealed that TNF-alpha triggered AP-1 and DNA binding and again, NS-398 and meloxicam inhibited this reaction via reducing c-Fos synthesis. Curcumin (AP-1 inhibitor) markedly suppressed the TNF-alpha-induced CCL2 expression. The immunohistochemical staining of NP surgical specimens also revealed an intimate alignment between CCL2-positive fibroblasts and CD-68-positive macrophages.

CONCLUSIONS:

These data suggest that NPFs may contribute to NP development by synthesizing CCL2 to promote macrophage recruitment. Furthermore, COX-2 facilitates CCL2 transcription in NPFs via a c-Fos and AP-1 signaling pathway.

• Authors: Chia-Tung Shun, Sze-Kwan Lin, Chi-Yuan Hong, Sang-Heng Kok, Yun-Hsiang Juan, Chih-Chiang Wang, Ming-Che Hsu, Chia-Ming Liu
• Journal: The Annals of otology, rhinology, and laryngology (Ann Otol Rhinol Laryngol) Vol. 114 Issue 11 Pg. 879-85 (Nov 2005) ISSN: 0003-4894 [Print] United States
• PMID: 16358608 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CCL2 protein, human
• Chemokine CCL2
• Prostaglandins
• Tumor Necrosis Factor-alpha
• Cyclooxygenase 2

Topics

• Cells, Cultured
• Chemokine CCL2 (biosynthesis, genetics)
• Cyclooxygenase 2 (physiology)
• Fibroblasts (metabolism)
• Humans
• Nasal Polyps (etiology)
• Prostaglandins (physiology)
• Tumor Necrosis Factor-alpha (physiology)