PMID- 9718198
OWN - NLM
STAT- MEDLINE
DCOM- 19981110
LR  - 20131121
IS  - 0884-0431 (Print)
IS  - 0884-0431 (Linking)
VI  - 13
IP  - 8
DP  - 1998 Aug
TI  - TNF-alpha increases expression of IL-6 and ICAM-1 genes through activation of 
      NF-kappaB in osteoblast-like ROS17/2.8 cells.
PG  - 1290-9
AB  - 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.
FAU - Kurokouchi, K
AU  - Kurokouchi K
AD  - Department of Endocrinology and Metabolism, Research Institute of Environmental 
      Medicine, Nagoya University, Japan.
FAU - Kambe, F
AU  - Kambe F
FAU - Yasukawa, K
AU  - Yasukawa K
FAU - Izumi, R
AU  - Izumi R
FAU - Ishiguro, N
AU  - Ishiguro N
FAU - Iwata, H
AU  - Iwata H
FAU - Seo, H
AU  - Seo H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Bone Miner Res
JT  - Journal of bone and mineral research : the official journal of the American 
      Society for Bone and Mineral Research
JID - 8610640
RN  - 0 (Free Radical Scavengers)
RN  - 0 (Interleukin-6)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/pharmacology
MH  - Animals
MH  - Bone Neoplasms
MH  - Cytosol/metabolism
MH  - Free Radical Scavengers/pharmacology
MH  - Intercellular Adhesion Molecule-1/*genetics
MH  - Interleukin-6/*genetics
MH  - NF-kappa B/*genetics/metabolism
MH  - Osteoblasts/*drug effects/metabolism
MH  - Osteosarcoma
MH  - RNA, Messenger/analysis/*metabolism
MH  - Rats
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 1998/08/26 00:00
MHDA- 1998/08/26 00:01
CRDT- 1998/08/26 00:00
PHST- 1998/08/26 00:00 [pubmed]
PHST- 1998/08/26 00:01 [medline]
PHST- 1998/08/26 00:00 [entrez]
AID - 10.1359/jbmr.1998.13.8.1290 [doi]
PST - ppublish
SO  - J Bone Miner Res. 1998 Aug;13(8):1290-9. doi: 10.1359/jbmr.1998.13.8.1290.