RRC ID |
39212
|
著者 |
Kurokouchi K, Kambe F, Yasukawa K, Izumi R, Ishiguro N, Iwata H, Seo H.
|
タイトル |
TNF-alpha increases expression of IL-6 and ICAM-1 genes through activation of NF-kappaB in osteoblast-like ROS17/2.8 cells.
|
ジャーナル |
J Bone Miner Res
|
Abstract |
Tumor necrosis factor-alpha (TNF-alpha) plays a key role in inflammatory diseases such as rheumatoid arthritis and in postmenopausal osteoporosis. In various tissues, TNF-alpha action is mediated by a transcription factor, nuclear factor-kappa B (NF-kappaB). However, little is known about how TNF-alpha exerts its action in osteoblasts. We thus examined the effect of TNF-alpha on the activation of NF-kappaB in rat osteoblast-like osteosarcoma cells (ROS17/2.8). Electrophoretic mobility shift assay revealed that the activation of the p50-p65 heterodimer NF-kappaB was induced by TNF-alpha as early as 15 minutes followed by a persistent activation for 48 h. When the binding activity of NF-kappaB in cytosol was examined using detergents that dissociate NF-kappaB from an inhibitory protein IkappaB, 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-alpha 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-alpha. These results suggest that the rapid activation of NF-kappaB by TNF-alpha is mainly due to the nuclear translocation of NF-kappaB pre-existing in cytosol, and that the subsequent increase in the expression of p50 and p65 may result in the persistent activation of NF-kappaB during TNF-alpha stimulation. TNF-alpha 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-alpha-dependent increase in these mRNAs, and simultaneously reduced the activation of NF-kappaB by TNF-alpha, indicating that NF-kappaB mediates the TNF-alpha-dependent expression of IL-6 and ICAM-1 in ROS17/2.8 cells. These results suggest that the activation of NF-kappaB by TNF-alpha 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.
|
巻・号 |
13(8)
|
ページ |
1290-9
|
公開日 |
1998-8-1
|
DOI |
10.1359/jbmr.1998.13.8.1290
|
PMID |
9718198
|
MeSH |
Acetylcysteine / pharmacology
Animals
Bone Neoplasms
Cytosol / metabolism
Free Radical Scavengers / pharmacology
Intercellular Adhesion Molecule-1 / genetics*
Interleukin-6 / genetics*
NF-kappa B / genetics*
NF-kappa B / metabolism
Osteoblasts / drug effects*
Osteoblasts / metabolism
Osteosarcoma
RNA, Messenger / analysis
RNA, Messenger / metabolism*
Rats
Tumor Cells, Cultured
Tumor Necrosis Factor-alpha / pharmacology*
|
IF |
5.854
|
引用数 |
88
|
WOS 分野
|
ENDOCRINOLOGY & METABOLISM
|
リソース情報 |
ヒト・動物細胞 |
ROS-17/2.8-5(RCB0462) |