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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2000-4-25
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pubmed:abstractText |
We recently showed that adenoviral transfer and expression of the Lps(d)/Ran gene isolated from endotoxin-resistant C3H/HeJ mice could protect endotoxin-sensitive mice from endotoxic shock. Elevation of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha), is thought to be essential for the development of septic shock. To investigate the extent to which Lps(d)/Ran affects TNF-alpha production, we transduced primary macrophages from endotoxin-sensitive and -resistant mice with adenoviral vectors expressing the wild-type and the mutant Lps/Ran cDNAs and other control genes, and compared the amount of TNF-alpha produced by these various transduced macrophages. Successful transfer and expression of Lps(d)/Ran cDNA in endotoxin-sensitive C3H/HeOuJ macrophages reduced TNF-alpha production upon lipopolysaccharide (LPS) stimulation, as compared with macrophages transduced with vectors expressing the wild-type Lps(n)/Ran cDNA, the green fluorescent protein gene, or the lacZ gene. On the other hand, successful transfer and expression of the wild-type Lps(n)/Ran cDNA in primary macrophages from endotoxin-resistant C3H/HeJ mice failed to induce TNF-alpha production to any significant extent unless a very high LPS concentration was used. Given our previous demonstration that Lps(n)/Ran functions effectively in restoring LPS responsiveness in B cells from C3H/HeJ mice, we conclude that Lps/Ran is involved in a CD14-independent signal transduction pathway. This dominant negative down-regulation by Lps(d)/Ran on TNF-alpha production by macrophages and probably other innate immune responses may be key to the development of an effective gene therapy for endotoxic or septic shock.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/10706609-101590,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10706609-10334979,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10706609-10359581,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10706609-10426323,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10706609-10500213,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10706609-1085749,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10706609-1730929,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10706609-202651,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10706609-2108320,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10706609-2469726,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10706609-3555304,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10706609-3764421,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10706609-3782828,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10706609-3883191,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10706609-3895437,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10706609-4138849,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10706609-4877918,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10706609-6384794,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10706609-7849398,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10706609-8387893,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10706609-8890215,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10706609-9127007,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10706609-9212113,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10706609-9359687,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10706609-9363937,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10706609-9510153,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10706609-9841923,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10706609-9851930,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10706609-9989974,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10706609-9989976
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
14
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pubmed:volume |
97
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2852-7
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:10706609-Adenoviridae,
pubmed-meshheading:10706609-Animals,
pubmed-meshheading:10706609-B-Lymphocytes,
pubmed-meshheading:10706609-Blotting, Western,
pubmed-meshheading:10706609-Cell Differentiation,
pubmed-meshheading:10706609-Cell Division,
pubmed-meshheading:10706609-Cell Line,
pubmed-meshheading:10706609-Cloning, Molecular,
pubmed-meshheading:10706609-DNA, Complementary,
pubmed-meshheading:10706609-Down-Regulation,
pubmed-meshheading:10706609-Endotoxins,
pubmed-meshheading:10706609-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:10706609-Genes, Dominant,
pubmed-meshheading:10706609-Humans,
pubmed-meshheading:10706609-Lipopolysaccharides,
pubmed-meshheading:10706609-Macrophages,
pubmed-meshheading:10706609-Mice,
pubmed-meshheading:10706609-Mice, Inbred C3H,
pubmed-meshheading:10706609-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:10706609-Tumor Necrosis Factor-alpha,
pubmed-meshheading:10706609-ran GTP-Binding Protein
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pubmed:year |
2000
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pubmed:articleTitle |
Dominant negative down-regulation of endotoxin-induced tumor necrosis factor alpha production by Lps(d)/Ran.
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pubmed:affiliation |
Department of Pathology and Laboratory Medicine, Fels Institute, Temple University School of Medicine, Philadelphia, PA 19140, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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