Dependence of NF-kappaB activation and free radical generation on silica-induced TNF-alpha production in macrophages.

作者: Yon Rojanasakul , Jiangping Ye , Fei Chen , Liying Wang , Ningli Cheng

DOI: 10.1023/A:1007051402840

关键词:

摘要: Tumor necrosis factor alpha (TNFalpha) plays an important role in the pathogenesis of silicosis and other chronic inflammatory lung diseases. The present study investigates nuclear transcription kappaB (NF-kappaB) oxygen free radicals silica-induced TNFalpha production primary alveolar macrophages RAW 264.7 cells. Using electrophoretic mobility shift assay (EMSA) enzyme-linked immunoadsorbent (ELISA), we have demonstrated that silica can induce NF-kappaB activation expression a dose-dependent manner. Transient transfection assays with plasmid construct containing binding sites linked to reporter gene further show is able transcriptional NF-kappaB-dependent gene. Inhibition by SN50, specific blocker, abolishes production. Pretreatment cells catalase (H2O2 scavenger) or deferoxamine (*OH effectively inhibits activation, whereas superoxide dismutase (O2 has opposite effect. These results indicate silica-mediated radical generation play roles expression.

参考文章(33)
K.L. Rhoades, S.H. Golub, J.S. Economou, The regulation of the human tumor necrosis factor alpha promoter region in macrophage, T cell, and B cell lines. Journal of Biological Chemistry. ,vol. 267, pp. 22102- 22107 ,(1992) , 10.1016/S0021-9258(18)41641-9
B Pipy, S Gossart, J Rami, C Cambon, C Orfila, P Carré, M H Séguélas, J C Lepert, Reactive oxygen intermediates as regulators of TNF-alpha production in rat lung inflammation induced by silica. Journal of Immunology. ,vol. 156, pp. 1540- 1548 ,(1996)
H Isshiki, S Akira, O Tanabe, T Nakajima, T Shimamoto, T Hirano, T Kishimoto, Constitutive and interleukin-1 (IL-1)-inducible factors interact with the IL-1-responsive element in the IL-6 gene. Molecular and Cellular Biology. ,vol. 10, pp. 2757- 2764 ,(1990) , 10.1128/MCB.10.6.2757
Yao-Zhong Lin, SongYi Yao, Ruth Ann Veach, Troy R. Torgerson, Jacek Hawiger, Inhibition of Nuclear Translocation of Transcription Factor NF-κB by a Synthetic Peptide Containing a Cell Membrane-permeable Motif and Nuclear Localization Sequence Journal of Biological Chemistry. ,vol. 270, pp. 14255- 14258 ,(1995) , 10.1074/JBC.270.24.14255
Bernd Krämer, Albrecht Meichle, Gabriele Hensel, Patrick Charnay, Martin Krönke, Characterization of an Krox-24/Egr-1-responsive Element in the Human Tumor Necrosis Factor Promoter Biochimica et Biophysica Acta. ,vol. 1219, pp. 413- 421 ,(1994) , 10.1016/0167-4781(94)90066-3
Dana Savici, Bei He, Lois J. Geist, Martha M. Monick, Gary W. Hunninghake, Silica Increases Tumor Necrosis Factor (TNF) Production, in Part, by Upregulating the TNF Promoter Experimental Lung Research. ,vol. 20, pp. 613- 625 ,(1994) , 10.3109/01902149409031740
Markus Meyer, Heike L. Pahl, Patrick A. Baeuerle, Regulation of the transcription factors NF-κB and AP-1 by redox changes Chemico-Biological Interactions. ,vol. 91, pp. 91- 100 ,(1994) , 10.1016/0009-2797(94)90029-9
Barry Halliwell, John M.C. Gutteridge, Oxygen free radicals and iron in relation to biology and medicine: some problems and concepts. Archives of Biochemistry and Biophysics. ,vol. 246, pp. 501- 514 ,(1986) , 10.1016/0003-9861(86)90305-X