These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Role of NFkappaB in the regulation of macrophage colony stimulating factor by tumor necrosis factor-alpha in ST2 bone stromal cells.
    Author: Isaacs SD, Fan X, Fan D, Gewant H, Murphy TC, Farmer P, Taylor WR, Nanes MS, Rubin J.
    Journal: J Cell Physiol; 1999 May; 179(2):193-200. PubMed ID: 10199558.
    Abstract:
    Expression of MCSF in bone is important to the regulation of osteoclastogenesis. We show here that tumor necrosis factor-alpha (TNFalpha) increases the production of both soluble (sMCSF) and membrane-bound (mMCSF) macrophage colony stimulating factor by ST2 bone stromal cells. Treatment of ST2 cells with TNFalpha caused sMCSF levels to increase by 394+/-5% from basal; mMCSF rose by 316+/-66% from 30+/-10 per 100,000 cells in the same time. These increases were consistent with increased expression of mRNAs encoding both isoforms. Increases in MCSF mRNA are also seen after stimulation with dexamethasone. To investigate the potential role of NFkappaB in this TNFalpha effect, we treated cells with sodium salicylate (NaS), an inhibitor of NFkappaB translocation. NaS decreased TNFalpha-stimulated NFkappaB activation by 50% as assessed by EMSA. Despite inhibition of NFkappaB signaling, NaS enhanced TNFalpha-stimulated MCSF secretion and did not prevent TNFalpha-stimulated increases in sMCSF mRNA, suggesting that NFkappaB was not involved in TNFalpha effect on the gene. TNFalpha failed to stimulate transcription of a 774 nucleotide MCSF promoter-luciferase reporter transfected into ST2 cells which contained the NFkappaB consensus sequence. Deletion of the seven nucleotides containing the NFkappaB homology response sequence from the MCSF promoter increased basal gene transcription by twofold. TNFalpha thus contributes to an osteoclastogenic environment through upregulation of bone expression of both MCSF isoforms. Our data suggests that NFkappaB is not the major signaling pathway through which this occurs.
    [Abstract] [Full Text] [Related] [New Search]