CHIA-TUNG SHUNSZE-KWAN LINHong C.-Y.SANG-HENG KOKJuan Y.-H.Wang C.-C.Hsu M.-C.Liu C.-M.2021-03-182021-03-1820050003-4894https://scholars.lib.ntu.edu.tw/handle/123456789/553273Objectives: 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 α (TNF-α) 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-α-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 I (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-α 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-α, whereas COX-2 inhibitors NS-398 and meloxicam abolished the up-regulation of c-Fos. The electrophoretic mobility shift assay revealed that TNF-α 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-α-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. ? 2005 Annals Publishing Company. All rights reserved.[SDGs]SDG3CD68 antigen; cyclooxygenase 2; cyclooxygenase 2 inhibitor; meloxicam; messenger RNA; monocyte chemotactic protein 1; n (2 cyclohexyloxy 4 nitrophenyl)methanesulfonamide; prostaglandin; protein c fos; protein c jun; transcription factor AP 1; tumor necrosis factor alpha; antigen expression; article; controlled study; fibroblast; gel mobility shift assay; gene expression; genetic transcription; human; human cell; human tissue; immunohistochemistry; in vivo study; inflammation; macrophage; Northern blotting; nose polyp; pathogenesis; priority journal; protein DNA interaction; protein protein interaction; signal transductionjournal article10.1177/000348940511401112163586082-s2.0-32544434542