Transcriptional regulation of increased CCL2 expression in pulmonary fibrosis involves nuclear factor-kappa B and activator protein-1

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	Transcriptional regulation of increased CCL2 expression in pulmonary fibrosis involves nuclear factor-kappa B and activator protein-1
	Deng, Xiaoling ; Xu, Mingyan ; Yuan, Chao ; Yin, Liqin ; Chen, Xihe ; Zhou, Xiaoqiong ; Li, Guanwu ; Fu, Yucai ; Feghali-Bostwick, Carol A. ; Pang, Linhua ; Deng XL(邓小玲)
刊名	http://dx.doi.org/10.1016/j.biocel.2013.04.003
	2013
关键词	MONOCYTE CHEMOATTRACTANT PROTEIN-1 SMOOTH-MUSCLE-CELLS LUNG FIBROBLAST PROLIFERATION HUMAN ENDOTHELIAL-CELLS CHEMOTACTIC PROTEIN-1 BRONCHOALVEOLAR LAVAGE GENE-EXPRESSION MESSENGER-RNA THROMBIN TISSUE
英文摘要	National Natural Science Foundation of China [30900661, 81072208]; Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry; Science Foundation of Shantou University Medical College; Basic Science and Clinical Research Foundation of Shantou University Medical College; Chemokine (CC motif) ligand-2 (CCL2) is a member of C-C chemokine superfamily that contributes to inflammatory and fibrotic process. Studies in patients and experimental animals provide compelling evidence that increased CCL2 expression plays an important role in the development of fibroproliferative lung disease. The up-regulated CCL2 expression in pulmonary fibrosis is also involved in the potent profibrotic effects that thrombin exerts during lung injury. Here, we investigated the transcriptional mechanism involved in CCL2 production by thrombin in human primary lung fibroblasts and explored the transcriptional mechanism of increased CCL2 expression in pulmonary fibrosis. Thrombin increased CCL2 mRNA levels but not mRNA stability, suggesting it was acting transcriptionally. The increased binding of transcription factors to nuclear factor-kappa B (NF-kappa B) and activator protein-1 (AP-1) elements in the CCL2 promoter contributed to active transcription following thrombin stimulation. Primary human lung fibroblasts isolated from patients with idiopathic pulmonary fibrosis (IPF) produced significantly higher levels of CCL2 than nonfibrotic lung fibroblasts. Furthermore, chromatin immunoprecipitation assays detected increased binding of NF-kappa B p65 and AP-1 subunit c-Jun to the CCL2 promoter of IPF cells both in the presence and absence of thrombin stimulation. The significantly increased binding of p65 and c-Jun to the CCL2 promoter was also observed in the lung tissue of bleomycin-induced pulmonary fibrosis murine model. Collectively, these findings strongly suggest that the increased binding of transcription factors to NF-kappa B and AP-1 elements in the CCL2 promoter is responsible for the active transcription expression of CCL2 in pulmonary fibrosis. (C) 2013 Elsevier Ltd. All rights reserved.
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/93528]
专题	医学院－已发表论文
推荐引用方式 GB/T 7714	Deng, Xiaoling,Xu, Mingyan,Yuan, Chao,et al. Transcriptional regulation of increased CCL2 expression in pulmonary fibrosis involves nuclear factor-kappa B and activator protein-1[J]. http://dx.doi.org/10.1016/j.biocel.2013.04.003,2013.
APA	Deng, Xiaoling.,Xu, Mingyan.,Yuan, Chao.,Yin, Liqin.,Chen, Xihe.,...&邓小玲.(2013).Transcriptional regulation of increased CCL2 expression in pulmonary fibrosis involves nuclear factor-kappa B and activator protein-1.http://dx.doi.org/10.1016/j.biocel.2013.04.003.
MLA	Deng, Xiaoling,et al."Transcriptional regulation of increased CCL2 expression in pulmonary fibrosis involves nuclear factor-kappa B and activator protein-1".http://dx.doi.org/10.1016/j.biocel.2013.04.003 (2013).