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rdf:type |
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lifeskim:mentions |
umls-concept:C0010453,
umls-concept:C0021755,
umls-concept:C0023810,
umls-concept:C0031307,
umls-concept:C0037083,
umls-concept:C0086418,
umls-concept:C0127400,
umls-concept:C0221928,
umls-concept:C0225336,
umls-concept:C0521009,
umls-concept:C0521447,
umls-concept:C1363844,
umls-concept:C1513475,
umls-concept:C1515877,
umls-concept:C1710082,
umls-concept:C1879547
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pubmed:issue |
12
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pubmed:dateCreated |
1999-4-15
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pubmed:abstractText |
Bacterial lipopolysaccharide (LPS)-mediated immune responses, including activation of monocytes, macrophages, and endothelial cells, play an important role in the pathogenesis of Gram-negative bacteria-induced sepsis syndrome. Activation of NF-kappaB is thought to be required for cytokine release from LPS-responsive cells, a critical step for endotoxic effects. Here we investigated the role and involvement of interleukin-1 (IL-1) and tumor necrosis factor (TNF-alpha) signal transducer molecules in LPS signaling in human dermal microvessel endothelial cells (HDMEC) and THP-1 monocytic cells. LPS stimulation of HDMEC and THP-1 cells initiated an IL-1 receptor-like NF-kappaB signaling cascade. In transient cotransfection experiments, dominant negative mutants of the IL-1 signaling pathway, including MyD88, IRAK, IRAK2, and TRAF6 inhibited both IL-1- and LPS-induced NF-kappaB-luciferase activity. LPS-induced NF-kappaB activation was not inhibited by a dominant negative mutant of TRAF2 that is involved in TNF signaling. LPS-induced activation of NF-kappaB-responsive reporter gene was not inhibited by IL-1 receptor antagonist. TLR2 and TLR4 were expressed on the cell surface of HDMEC and THP-1 cells. These findings suggest that a signal transduction molecule in the LPS receptor complex may belong to the IL-1 receptor/toll-like receptor (TLR) super family, and the LPS signaling cascade uses an analogous molecular framework for signaling as IL-1 in mononuclear phagocytes and endothelial cells.
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pubmed:grant |
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Differentiation,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1 Receptor-Associated...,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/MYD88 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Myeloid Differentiation Factor 88,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/TNF Receptor-Associated Factor 6
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
19
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pubmed:volume |
274
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7611-4
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:10075645-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:10075645-Amino Acid Sequence,
pubmed-meshheading:10075645-Antigens, Differentiation,
pubmed-meshheading:10075645-Cells, Cultured,
pubmed-meshheading:10075645-Endothelium,
pubmed-meshheading:10075645-Humans,
pubmed-meshheading:10075645-Interleukin-1,
pubmed-meshheading:10075645-Interleukin-1 Receptor-Associated Kinases,
pubmed-meshheading:10075645-Lipopolysaccharides,
pubmed-meshheading:10075645-Molecular Sequence Data,
pubmed-meshheading:10075645-Monocytes,
pubmed-meshheading:10075645-Myeloid Differentiation Factor 88,
pubmed-meshheading:10075645-NF-kappa B,
pubmed-meshheading:10075645-Protein Kinases,
pubmed-meshheading:10075645-Proteins,
pubmed-meshheading:10075645-Receptors, Immunologic,
pubmed-meshheading:10075645-Signal Transduction,
pubmed-meshheading:10075645-Skin,
pubmed-meshheading:10075645-TNF Receptor-Associated Factor 6,
pubmed-meshheading:10075645-Transfection
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pubmed:year |
1999
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pubmed:articleTitle |
Bacterial lipopolysaccharide activates nuclear factor-kappaB through interleukin-1 signaling mediators in cultured human dermal endothelial cells and mononuclear phagocytes.
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pubmed:affiliation |
Division of Pediatric Infectious Diseases, Ahmanson Department of Pediatrics, Steven Spielberg Pediatric Research Center, Cedars-Sinai Medical Center and UCLA School of Medicine, Los Angeles, California 90048, 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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