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This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Yamato, K. Articles by Koeffler, H. P. Search for Related Content PubMed PubMed Citation Articles by Yamato, K. Articles by Koeffler, H. P. Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Granulocyte-macrophage colony-stimulating factor: signals for its mRNA accumulation K Yamato, Z El-Hajjaoui, JF Kuo and HP Koeffler UCLA Department of Medicine, Los Angeles, CA 90024-1678. Granulocyte-monocyte colony-stimulating factor (GM-CSF) is an important hematopoietic growth factor. Mesenchymal cells produce abundant GM-CSF in response to tumor necrosis factor alpha (TNF). We wished to determine (1) what cellular pathways enhanced levels of GM-CSF mRNA, and (2) if TNF used any of these pathways. Modulation in levels of GM- CSF mRNA in human fibroblasts (WI-38) was studied by using Northern blot analysis. Markedly increased levels of GM-CSF mRNA occurred in these cells after exposure to sodium fluoride (NaF) and the effect of NaF was slightly enhanced by aluminum chloride; these results suggest that accumulation of GM-CSF mRNA can occur by activating a G-binding protein. Stimulators of protein kinase C dramatically increased levels of GM-CSF mRNA; however, blockade of protein kinase C activity did not attenuate accumulation of GM-CSF mRNA stimulated by TNF and NaF. Exposure to ouabain increased levels of GM-CSF mRNA and this effect was prominently enhanced in the presence of low concentrations of extracellular K+ and was almost abolished in high concentrations of extracellular K+. A monovalent ionophore (monensin) also increased levels of GM-CSF mRNA. Both ouabain and monensin can increase intracellular Ca++ concentration (Cai++) through Na+-Ca++ exchange. A calcium channel blocker (diltiazem) blocked the increased levels of GM- CSF mRNA mediated by ouabain, but could not block the stimulation mediated by TNF alpha. Ca++ ionophores also increased levels of GM-CSF mRNA and rapidly increased levels of Cai++. TNF did not increase Cai++ and, moreover, was able to stimulate accumulation of GM-CSF mRNA in the absence of extracellular Ca++. Taken together, we have found that several different cellular pathways can lead to prominent accumulation of GM-CSF mRNA in mesenchymal cells including (1) activation of protein kinase C, (2) increase in Cai++, and (3) stimulation of G-binding protein. Our studies show that TNF appears to increase levels of GM-CSF mRNA independent of protein kinase C activity or levels of Cai++. Volume 74, Issue 4, pp. 1314-1320, 09/01/1989 Copyright © 1989 by The American Society of Hematology CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Matsumori, K. Ono, R. Nishio, H. Igata, B Pharm, T. Shioi, S. Matsui, Y. Furukawa, A. Iwasaki, Y. Nose, et al. Modulation of Cytokine Production and Protection Against Lethal Endotoxemia by the Cardiac Glycoside Ouabain Circulation, September 2, 1997; 96(5): 1501 - 1506. [Abstract] [Full Text]

	Copyright © 1989 by American Society of Hematology         Online ISSN: 1528-0020