Vitamin C inhibits granulocyte macrophage-colony-stimulating factor-induced signaling pathways Journal Article
| Authors: | Cárcamo, J. M.; Bórquez-Ojeda, O.; Golde, D. W. |
| Article Title: | Vitamin C inhibits granulocyte macrophage-colony-stimulating factor-induced signaling pathways |
| Abstract: | Vitamin C is present in the cytosol as ascorbic acid, functioning primarily as a cofactor for enzymatic reactions and as an antioxidant to scavenge free radicals. Human granulocyte macrophage-colony-stimulating factor (GM-CSF) induces an increase in reactive oxygen species (ROS) and uses ROS for some signaling functions. We therefore investigated the effect of vitamin C on GM-CSF-mediated responses. Loading U937 cells with vitamin C decreased intracellular levels of ROS and inhibited the production of ROS induced by GM-CSF. Vitamin C suppressed GM-CSF-dependent phosphorylation of the signal transducer and activator of transcription 5 (Stat-5) and mitogen-activated protein (MAP) kinase (Erk1 and Erk2) in a dose-dependent manner as was phosphorylation of MAP kinase induced by both interleukin 3 (IL-3) and GM-CSF in HL-60 cells. In 293T cells transfected with alpha and beta GM-CSF receptor subunits (αGMR and βGMR), GM-CSF-induced phosphorylation of βGMR and Jak-2 activation was suppressed by vitamin C loading. GM-CSF-mediated transcriptional activation of a luciferase reporter construct containing STAT-binding sites was also inhibited by vitamin C. These results substantiate the importance of ROS in GM-CSF signaling and indicate a role for vitamin C in downmodulating GM-CSF signaling responses. Our findings point to vitamin C as a regulator of cytokine redox-signal transduction in host defense cells and a possible role in controlling inflammatory responses. © 2002 by The American Society of Hematology. |
| Keywords: | signal transduction; mitogen activated protein kinase; controlled study; protein phosphorylation; human cell; dna-binding proteins; cell proliferation; cell division; transcription initiation; granulocyte macrophage colony stimulating factor; luciferase; inflammation; enzyme activation; tumor cells, cultured; phosphorylation; drug antagonism; immune response; genetic transfection; drug mechanism; drug uptake; janus kinase; reporter gene; reactive oxygen species; reactive oxygen metabolite; binding site; trans-activators; ascorbic acid; bone marrow cell; monocyte; adjuvants, immunologic; homeostasis; mitogen-activated protein kinases; stat5 protein; stat5 transcription factor; megakaryocyte; dehydroascorbic acid; oxidation reduction reaction; concentration response; granulocyte-macrophage colony-stimulating factor; kidney cell; interleukin 3; casein kinase ii; granulocyte macrophage colony stimulating factor receptor; receptors, granulocyte-macrophage colony-stimulating factor; receptor subunit; milk proteins; humans; human; priority journal; article |
| Journal Title: | Blood |
| Volume: | 99 |
| Issue: | 9 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2002-05-01 |
| Start Page: | 3205 |
| End Page: | 3212 |
| Language: | English |
| DOI: | 10.1182/blood.V99.9.3205 |
| PUBMED: | 11964284 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
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