https://scholars.lib.ntu.edu.tw/handle/123456789/553231
標題: | Tumor necrosis factor-α stimulates the expression of C-C chemokine ligand 2 gene in fibroblasts from the human nasal polyp through the pathways of mitogen-activated protein kinase | 作者: | SZE-KWAN LIN SANG-HENG KOK CHIA-TUNG SHUN Hong C.-Y. Wang C.-C. Hsu M.-C. Liu C.-M. |
公開日期: | 2007 | 卷: | 21 | 期: | 2 | 起(迄)頁: | 251-255 | 來源出版物: | American Journal of Rhinology | 摘要: | Background: Recruitment of macrophages is crucial to the pathogenesis of the nasal polyp (NP) because this disease is believed to be inflammation related. Information regarding the expression of C-C chemokine ligand 2 (CCL2), an essential modulator of monocyte chemotaxis in nasal polyp fibroblasts (NPFs), remains unavailable. In this study, the effects of tumor necrosis factor (TNF)-α on CCL2 expression in NPFs and the signaling pathway involved were investigated. Methods: Primary cultures of NPFs were established from NPs. The expressions of CCL2, c-Fos, and c-Jun mRNAs in NPF after TNF-α stimulation were detected by Northern blot. Western blot was used to examine the activation of mitogen-activated protein kinase (MAPK) signaling pathways. Activator protein (AP) 1/DNA interactions were evaluated by electrophoretic mobility shift assay (EMSA). Results: Northern blot showed that TNF-α stimulated CCL2 gene expression in NPFs. Significant increase of B-Raf, phosphorated MAPK including mitogen-activated ERK-activate kinase (MEK)1/2, extracellular signal-related kinase 1/2, and p38 were detected by Western blot. c-Fos and c-Jun mRNAs were induced by TNF-α, and PD98059 (MEK inhibitor) and SB203580 (p38 inhibitor) abolished the up-regulation of c-Fos. EMSA revealed that TNF-α increased AP-1/DNA binding, and PD98059 and SB203580 attenuated this reaction, possibly via reducing c-Fos synthesis. PD98059 and curcumin (AP-1 inhibitor) markedly suppressed the TNF-α-induced CCL2 expression, whereas the effect of SB203580 was less noted. Conclusion: TNF-α induces CCL2 transcription in NPFs. B-Raf/MEK/ERK signaling cascade and to a less extent the p38 pathway are responsible for c-Fos activation and the subsequent AP-1/DNA interaction leading to CCL2 expression. Copyright ? 2007, OceanSide Publications, Inc. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/553231 | ISSN: | 1050-6586 | DOI: | 10.2500/ajr.2007.21.2958 | SDG/關鍵字: | 2 (2 amino 3 methoxyphenyl)chromone; 4 (4 fluorophenyl) 2 (4 methylsulfinylphenyl) 5 (4 pyridyl)imidazole; B Raf kinase; curcumin; messenger RNA; mitogen activated protein kinase 1; mitogen activated protein kinase 3; mitogen activated protein kinase p38; monocyte chemotactic protein 1; protein c fos; protein c jun; transcription factor AP 1; tumor necrosis factor alpha; article; cell culture; cell stimulation; controlled study; enzyme activation; enzyme phosphorylation; fibroblast; gel mobility shift assay; human; human cell; human tissue; Northern blotting; nose polyp; protein DNA binding; protein DNA interaction; protein expression; protein synthesis; signal transduction; upregulation; Western blotting; Blotting, Northern; Blotting, Western; Cells, Cultured; Chemokine CCL2; Fibroblasts; Gene Expression; Genes, fos; Genes, jun; Humans; MAP Kinase Kinase Kinase 1; MAP Kinase Kinase Kinase 2; MAP Kinase Signaling System; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases; Nasal Polyps; p38 Mitogen-Activated Protein Kinases; Proto-Oncogene Proteins B-raf; Signal Transduction; Transcription Factor AP-1; Tumor Necrosis Factor-alpha |
顯示於: | 法醫學科所 |
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