Source:http://linkedlifedata.com/resource/pubmed/id/17016618
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rdf:type | |
lifeskim:mentions |
umls-concept:C0007634,
umls-concept:C0026473,
umls-concept:C0037083,
umls-concept:C0086418,
umls-concept:C0205263,
umls-concept:C0851285,
umls-concept:C1167322,
umls-concept:C1456820,
umls-concept:C1554184,
umls-concept:C1555029,
umls-concept:C1709059,
umls-concept:C1710082,
umls-concept:C1749467,
umls-concept:C1879547,
umls-concept:C2752508
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pubmed:issue |
5
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pubmed:dateCreated |
2006-10-3
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pubmed:abstractText |
Transmembrane tumor necrosis factor-alpha (mTNF-alpha) is known to be the precursor of soluble TNF-alpha (sTNF-alpha). mTNF-alpha can act as a ligand on the TNF receptor- (TNFR)- bearing cell through 'forward signaling' or as a receptor on the TNF producing cell through 'reverse signaling'. In the current study, we investigated the role of mTNF-alpha-mediated reverse signaling in regulating sTNF-alpha-induced activation of human monocytic U937 cells. We demonstrated that pretreatment with sTNFRI, for inducing reverse signaling through mTNF-alpha, sensitized U937 cells to sTNF-alpha stimulation, as evidenced by an increase in reactive oxygen production and mRNA levels of proinflammatory cytokines (TNF-alpha, IL-1beta, and IL-8) in these cells. Further experiments revealed that IkappaB-alpha degradation was increased in the monocytic cells primed with sTNFRI, implying that reverse signaling of mTNF-alpha sensitizes U937 cells via an NF-kappaB-dependent mechanism. On the other hand, binding of sTNFRI to mTNF-alpha after sTNF-alpha-induced activation of U937 cells reduced mRNA stability (half-life) of IL-1beta and IL-8. The involvement of reverse signaling in the process was verified by using a mutated form of mTNF-alpha lacking the majority of the cytoplasmic domain. Our results clearly showed that enhanced mRNA degradation of the cytokines occurred only in U937 cells transfected with a wild-type mTNF-alpha, but not in those cells transfected with the mutant mTNF-alpha. Taken together, these data suggest that reverse signaling through mTNF-alpha may exert a double role in modulating sTNF-alpha bioactivity. It is positive when reverse signaling occurs prior to sTNF-alpha stimulation, while it is negative when reverse signaling occurs after the sTNF-alpha signal. Thus, our findings strengthen a role of mTNF-alpha-mediated reverse signaling in the regulation of immune-inflammatory response and control of inflammatory reaction.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-8,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappaB inhibitor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1107-3756
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
885-92
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pubmed:meshHeading |
pubmed-meshheading:17016618-Cell Line, Tumor,
pubmed-meshheading:17016618-Cell Membrane,
pubmed-meshheading:17016618-Humans,
pubmed-meshheading:17016618-I-kappa B Proteins,
pubmed-meshheading:17016618-Interleukin-1,
pubmed-meshheading:17016618-Interleukin-8,
pubmed-meshheading:17016618-Macrophage Activation,
pubmed-meshheading:17016618-Monocytes,
pubmed-meshheading:17016618-RNA, Messenger,
pubmed-meshheading:17016618-Reactive Oxygen Species,
pubmed-meshheading:17016618-Receptors, Tumor Necrosis Factor,
pubmed-meshheading:17016618-Signal Transduction,
pubmed-meshheading:17016618-Tumor Necrosis Factor-alpha,
pubmed-meshheading:17016618-U937 Cells
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pubmed:year |
2006
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pubmed:articleTitle |
Dual regulation of soluble tumor necrosis factor-alpha induced activation of human monocytic cells via modulating transmembrane TNF-alpha-mediated 'reverse signaling'.
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pubmed:affiliation |
Department of Immunology, Tongji Medical College, Central China University of Science and Technology, Wuhan 430030, PR China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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