| Glycolytic control of adjuvant-induced macrophage survival: role of PI3K, MEK1/2, and Bcl-2. | |
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MedLine Citation:
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PMID: 19270084 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Uptake by macrophages forms an important part of the mode of action of particulate adjuvants such as oil-in-water emulsions and alum. We have found previously that such adjuvants promote macrophage survival and suggested that this response may contribute to their efficacy. To explore this adjuvant activity further, we have investigated whether oil-in-water emulsion stimulates glucose uptake in macrophages and whether such uptake is relevant to the promotion of survival. We found that oil-in-water emulsion stimulated glucose uptake in a biphasic manner. The first acute phase was independent of mRNA and protein synthesis but appeared to require PI3K activity. In contrast, the second chronic phase was dependent on mRNA and protein synthesis. Importantly, the second phase of glucose uptake required MEK1/2 as well as PI3K activity, indicating that the MEK1/2 pathway can also contribute to cellular glucose uptake. The increased glucose transporter 1 expression during the second phase and long-term survival also appeared to be dependent on PI3K and MEK1/2 signaling pathways. Metabolism of the glucose was required for the emulsion-stimulated survival as well as the increase of prosurvival Bcl-2 transcript levels and maintenance of Bcl-2 protein expression. As transgenic overexpression of Bcl-2 enhances the survival of macrophages in the absence of growth factor, the glycolytic control of Bcl-2 levels may play a central role in emulsion-stimulated macrophage survival. Enhanced glucose uptake by macrophages may therefore be critical to the action of particulate adjuvants. |
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Authors:
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Margaret Chang; John A Hamilton; Glen M Scholz; Caryn L Elsegood |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-03-06 |
Journal Detail:
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Title: Journal of leukocyte biology Volume: 85 ISSN: 1938-3673 ISO Abbreviation: J. Leukoc. Biol. Publication Date: 2009 Jun |
Date Detail:
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Created Date: 2009-06-02 Completed Date: 2009-06-17 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 8405628 Medline TA: J Leukoc Biol Country: United States |
Other Details:
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Languages: eng Pagination: 947-56 Citation Subset: IM |
Affiliation:
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The University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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1-Phosphatidylinositol 3-Kinase
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metabolism* Adjuvants, Immunologic / pharmacology* Animals Cell Survival / drug effects Emulsions / pharmacology Gene Expression Regulation / drug effects Glucose / metabolism Glucose Transporter Type 1 / metabolism Glycolysis / drug effects* Humans MAP Kinase Kinase 1 / metabolism MAP Kinase Kinase 2 / metabolism Macrophages / cytology*, drug effects, enzymology* Mice Mitogen-Activated Protein Kinase Kinases / metabolism* Protein Biosynthesis / drug effects Protein Stability / drug effects Proto-Oncogene Proteins c-bcl-2 / genetics, metabolism* RNA, Messenger / genetics, metabolism Transcription, Genetic / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Adjuvants, Immunologic; 0/Emulsions; 0/Glucose Transporter Type 1; 0/Proto-Oncogene Proteins c-bcl-2; 0/RNA, Messenger; 0/Slc2a1 protein, mouse; 50-99-7/Glucose; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.12.2/MAP Kinase Kinase 1; EC 2.7.12.2/MAP Kinase Kinase 2; EC 2.7.12.2/Mitogen-Activated Protein Kinase Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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