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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
1994-6-24
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pubmed:abstractText |
The highly regulated enzyme HMG-CoA reductase generates mevalonate, the precursor of a complex series of isoprenoids that posttranslationally modify (isoprenylate) certain proteins (e.g., the low-molecular-weight GTP-binding proteins) or that are incorporated into cholesterol and other end products. We recently reported that isoprenoids are required for NADPH oxidase activity in granulocytes via LMW GTP-binding protein isoprenylation. In this study, we evaluated the effects of isoprenoid depletion on the expression of proinflammatory genes in human monocytic THP-1 cells. We selected conditions under which pretreatment for 24 h with isoprenoid synthesis inhibitors (HMG-CoA reductase inhibitor lovastatin or compactin at 10 microM) did not compromise cell viability but markedly suppressed H2O2 generation. Under these conditions interleukin-8 (IL-8) production was attenuated (by 50-90%) in response to lipopolysaccharide, granulocyte-macrophage colony-stimulating factor, and phorbol myristate acetate. Coincubation of reductase inhibitor-treated cells with mevalonate prevented the attenuation of IL-8 production by reductase inhibitors. The effects of isoprenoid depletion on cytokine production were selective: IL-1 beta generation was not inhibited but the production of IL-6 and IL-8 was concomitantly suppressed. IL-8 induction was suppressed at least in part through attenuation of the increase in mRNA in stimulated cells. We conclude that isoprenoid generation through the mevalonate pathway is a requirement for IL-8 induction by activated monocytic cells in vitro. Isoprenylation inhibitors have the potential to alter monocyte proinflammatory function.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Granulocyte-Macrophage...,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxymethylglutaryl-CoA...,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-8,
http://linkedlifedata.com/resource/pubmed/chemical/Lovastatin,
http://linkedlifedata.com/resource/pubmed/chemical/Mevalonic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/compactin
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0741-5400
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
55
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
749-55
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:8195701-Cell Division,
pubmed-meshheading:8195701-Cell Line,
pubmed-meshheading:8195701-Cell Survival,
pubmed-meshheading:8195701-GTP-Binding Proteins,
pubmed-meshheading:8195701-Gene Expression,
pubmed-meshheading:8195701-Granulocyte-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:8195701-Humans,
pubmed-meshheading:8195701-Hydroxymethylglutaryl-CoA Reductase Inhibitors,
pubmed-meshheading:8195701-Interleukin-8,
pubmed-meshheading:8195701-Lovastatin,
pubmed-meshheading:8195701-Mevalonic Acid,
pubmed-meshheading:8195701-Monocytes,
pubmed-meshheading:8195701-Protein Prenylation,
pubmed-meshheading:8195701-Protein Processing, Post-Translational,
pubmed-meshheading:8195701-Tetradecanoylphorbol Acetate
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pubmed:year |
1994
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pubmed:articleTitle |
Role of the mevalonate pathway of isoprenoid synthesis in IL-8 generation by activated monocytic cells.
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pubmed:affiliation |
Veterans Affairs Medical Center, San Diego, California 92161.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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