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In various tissues, TNF-\u03b1 action is mediated by a transcription factor, nuclear factor-kappa B (NF-\u03baB). However, little is known about how TNF-\u03b1 exerts its action in osteoblasts. We thus examined the effect of TNF-\u03b1 on the activation of NF-\u03baB in rat osteoblast-like osteosarcoma cells (ROS17\/2.8). Electrophoretic mobility shift assay revealed that the activation of the p50-p65 heterodimer NF-\u03baB was induced by TNF-\u03b1 as early as 15 minutes followed by a persistent activation for 48 h. When the binding activity of NF-\u03baB in cytosol was examined using detergents that dissociate NF-\u03baB from an inhibitory protein I\u03baB, it decreased during the initial 30 minutes and then increased to the unstimulated level. Northern blot analysis revealed a marked increase in the mRNA levels of p105, a precursor of p50, 6 h after TNF-\u03b1 and a gradual increase in p65 mRNA levels during the initial 1 h. Significant increase in both mRNA levels continued until 24 h after TNF-\u03b1. These results suggest that the rapid activation of NF-\u03baB by TNF-\u03b1 is mainly due to the nuclear translocation of NF-\u03baB pre-existing in cytosol, and that the subsequent increase in the expression of p50 and p65 may result in the persistent activation of NF-\u03baB during TNF-\u03b1 stimulation. TNF-\u03b1 also increased the mRNA levels of interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1). An antioxidant, N-acetyl-L-cysteine, significantly attenuated the TNF-\u03b1\u2013dependent increase in these mRNAs, and simultaneously reduced the activation of NF-\u03baB by TNF-\u03b1, indicating that NF-\u03baB mediates the TNF-\u03b1\u2013dependent expression of IL-6 and ICAM-1 in ROS17\/2.8 cells. These results suggest that the activation of NF-\u03baB by TNF-\u03b1 may play an important role in the production of cytokines and cell adhesion molecules from osteoblasts, leading to the promotion of bone resorption and inflammation.<\/jats:p>","DOI":"10.1359\/jbmr.1998.13.8.1290","type":"journal-article","created":{"date-parts":[[2006,4,26]],"date-time":"2006-04-26T19:48:37Z","timestamp":1146080917000},"page":"1290-1299","source":"Crossref","is-referenced-by-count":112,"title":["TNF-\u03b1 Increases Expression of IL-6 and ICAM-1 Genes Through Activation of NF-\u03baB in Osteoblast-like ROS17\/2.8 Cells"],"prefix":"10.1093","volume":"13","author":[{"given":"Kazutoshi","family":"Kurokouchi","sequence":"first","affiliation":[{"name":"Department of Orthopedics, Nagoya University School of Medicine, Nagoya, Japan"},{"name":"Department of Endocrinology and Metabolism, Division of Molecular and Cellular Adaptation, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fukushi","family":"Kambe","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Division of Molecular and Cellular Adaptation, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kou","family":"Yasukawa","sequence":"additional","affiliation":[{"name":"Japan Space Utilization Promotion Center, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryutaro","family":"Izumi","sequence":"additional","affiliation":[{"name":"Japan Space Utilization Promotion Center, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Ishiguro","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Nagoya University School of Medicine, Nagoya, 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