Osteoblast-derived TGF-beta1 stimulates IL-8 release through AP-1 and NF-kappaB in human cancer cells

中國醫藥大學機構典藏 China Medical University Repository, Taiwan > 中醫學院 > 中醫學系暨碩博班 > 期刊論文 > Item 310903500/3027

jsp.display-item.identifier=請使用永久網址來引用或連結此文件: http://ir.cmu.edu.tw/ir/handle/310903500/3027

题名:	Osteoblast-derived TGF-beta1 stimulates IL-8 release through AP-1 and NF-kappaB in human cancer cells
作者:	馮逸卿(Yi-Chin Fong);馬明琪(Maa Ming-Chei);蔡輔仁(Fuu-Jen Tsai);陳汶吉(Chen Wen-Chi);林昭庚(Jaung-Geng Lin);鄭隆賓(Long-Bin Jeng);楊榮森(Rong-Sen Yang);符文美(Wen-Mei Fu);湯智昕(Tang Chih-Hsin)*
贡献者:	中醫學院中醫學系學士班中醫外傷學科;中國附醫骨科部
日期:	2008-06
上传时间:	2009-08-20 17:58:35 (UTC+8)
摘要:	INTRODUCTION: The bone marrow microenvironment is further enriched by growth factors released during osteoclastic bone resorption. It has been reported that the chemokine interleukin (IL)-8 is a potent and direct activator of osteoclastic differentiation and bone resorption. However, the effect of bone-derived growth factors on the IL-8 production in human cancer cells and the promotion of osteoclastogenesis are largely unknown. The aim of this study was to investigate whether osteoblast-derived TGF-beta1 is associated with osteolytic bone diseases. MATERIALS AND METHODS: IL-8 mRNA levels were measured using RT-PCR analysis. MAPK phosphorylation was examined using the Western blot method. siRNA was used to inhibit the expression of TGF-beta1, BMP-2, and IGF-1. DNA affinity protein-binding assay and chromatin immunoprecipitation assays were used to study in vitro and in vivo binding of c-fos, c-jun, p65, and p50 to the IL-8 promoter. A transient transfection protocol was used to examine IL-8, NF-kappaB, and activator protein (AP)-1 activity. RESULTS: Osteoblast conditioned medium (OBCM) induced activation of IL-8, AP-1, and NF-kappaB promoter in human cancer cells. Osteoblasts were transfected with TGF-beta1, BMP-2, or IGF-1 small interfering RNA, and the medium was collected after 48 h. TGF-beta1 but not BMP-2 or IGF-1 siRNA inhibited OBCM-induced IL-8 release in human cancer cells. In addition, TGF-beta1 also directly induced IL-8 release in human cancer cells. Activation of AP-1 and NF-kappaB DNA-protein binding and MAPKs after TGF-beta1 treatment was shown, and TGF-beta1-induced IL-8 promoter activity was inhibited by the specific inhibitors of MAPK cascades. CONCLUSIONS: In this study, we provide evidence to show that the osteoblasts release growth factors, including TGF-beta1, BMP-2, and IGF-1. TGF-beta1 is the major contributor to the activation of extracellular signal-related kinase (ERK), p38, and c-Jun N-terminal kinase (JNK), leading to the activation of AP-1 and NF-kappaB on the IL-8 promoter and initiation of IL-8 mRNA and protein release, thereby promoting osteoclastogenesis.
關聯:	JOURNAL OF BONE AND MINERAL RESEARCH 23(6):961~970
显示于类别:	[中醫學系暨碩博班] 期刊論文

文件中的档案:

档案	大小	格式	浏览次数
	58Kb	Unknown	364	检视/开启

在CMUR中所有的数据项都受到原著作权保护.

TAIR相关文章

数据加载中.....