| Interferon regulatory factor-8-driven myeloid differentiation is regulated by 12/15-lipoxygenase-mediated redox signaling. | |
| | |
MedLine Citation:
|
PMID: 20647030 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
OBJECTIVE: Several transcription factors determine the cell fate decision between granulocytes and monocytes, but the upstream signal transduction pathways that govern myelopoiesis are largely unknown. Based on our observation of aberrant myeloid cell representation in hematopoietic tissues of 12/15-lipoxygenase (12/15-LOX)-deficient (Alox15) mice, we tested the hypothesis that polyunsaturated fatty acid metabolism regulates myelopoiesis. MATERIALS AND METHODS: Multicolor flow cytometric analysis and methylcellulose assays were used to compare myelopoiesis and the differentiative capacity of progenitors from Alox15 and wild-type mice. Furthermore, we elucidated the mechanism by which 12/15-LOX is involved in regulation of myelopoiesis. RESULTS: Granulopoiesis in Alox15 mice is increased while monopoiesis is reduced. Moreover, there is an accumulation of granulocyte-macrophage progenitors that exhibit defective differentiation. Mechanistically, we demonstrate that transcriptional activity of interferon regulatory factor-8 (Irf8), which regulates myelopoiesis, is impaired in Alox15 progenitors and bone marrow-derived macrophages due to loss of 12/15-LOX-mediated redox regulation of Irf8 nuclear accumulation. Restoration of redox signaling in Alox15 bone marrow cells and granulocyte-macrophage progenitors reversed the defect in myeloid differentiation. CONCLUSIONS: These data establish 12/15-LOX-mediated redox signaling as a novel regulator of myelopoiesis and Irf8. |
| | |
Authors:
|
Michelle Kinder; James E Thompson; Cong Wei; Suresh G Shelat; Ian A Blair; Martin Carroll; Ellen Puré |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-07-18 |
Journal Detail:
|
Title: Experimental hematology Volume: 38 ISSN: 1873-2399 ISO Abbreviation: Exp. Hematol. Publication Date: 2010 Nov |
Date Detail:
|
Created Date: 2010-10-22 Completed Date: 2010-12-30 Revised Date: 2011-06-14 |
Medline Journal Info:
|
Nlm Unique ID: 0402313 Medline TA: Exp Hematol Country: Netherlands |
Other Details:
|
Languages: eng Pagination: 1036-1046.e1-4 Citation Subset: IM |
Copyright Information:
|
Copyright © 2010 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved. |
Affiliation:
|
The Wistar Institute, Philadelphia, PA 19104, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Arachidonate 12-Lipoxygenase / deficiency*, genetics Arachidonate 15-Lipoxygenase / deficiency*, genetics Cell Differentiation / drug effects Cell Nucleus / metabolism Erythropoietin / pharmacology Female Flow Cytometry Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology Granulocyte-Macrophage Progenitor Cells / cytology, metabolism Granulocytes / cytology, metabolism Immunoblotting Interferon Regulatory Factors / metabolism* Interleukin-3 / pharmacology Interleukin-6 / pharmacology Macrophages / cytology, metabolism Male Mice Mice, Inbred C57BL Mice, Knockout Monocytes / cytology, metabolism Myeloid Progenitor Cells / cytology, metabolism* Myelopoiesis / drug effects Oxidation-Reduction Reactive Oxygen Species / metabolism Signal Transduction* |
| Grant Support | |
ID/Acronym/Agency:
|
P30 ES013508-039001/ES/NIEHS NIH HHS; P30CA10815/CA/NCI NIH HHS; P30ES013508/ES/NIEHS NIH HHS; R01 CA091016-09/CA/NCI NIH HHS; R01CA091016/CA/NCI NIH HHS; T32CA09171/CA/NCI NIH HHS; T32GM07229/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/12-15-lipoxygenase; 0/Interferon Regulatory Factors; 0/Interleukin-3; 0/Interleukin-6; 0/Reactive Oxygen Species; 0/interferon regulatory factor-8; 11096-26-7/Erythropoietin; 83869-56-1/Granulocyte-Macrophage Colony-Stimulating Factor; EC 1.13.11.31/Arachidonate 12-Lipoxygenase; EC 1.13.11.33/Arachidonate 15-Lipoxygenase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Aqueous extract of ginger shows antiproliferative activity through disruption of microtubule network...
Next Document: Pitch body orientation influences the perception of self-motion direction induced by optic flow.