Source:http://linkedlifedata.com/resource/pubmed/id/18021366
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
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| pubmed:dateCreated |
2007-11-20
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| pubmed:abstractText |
OK-432, penicillin-killed Streptococcus pyogenes, is used in treating lymphangiomas and carcinomas. We have studied proinflammatory interleukin (IL) secretion following OK-432 stimulation of total blood, peripheral blood mononuclear cell (PBMC) and purified monocytes in vitro. OK-432 stimulation of purified monocytes gave IL-1beta, IL-1RA, IL-6, IL-12p40 and tumour necrosis factor (TNF)-alpha response. OK-432 stimulation of cells within blood did, however, not yield TNF-alpha secretion. When PBMC or monocytes were cultured in low-attachment wells a decreased IL secretion was observed compared to adherent cells. Inhibition of Syk kinase with piceatannol, only at high, non-specific doses, but not PI3 kinase inhibition with LY294002 or Wortmannin, decreased monocyte IL response to OK-432. This shows that beta(1-3)-integrin receptor function is not necessary for monocyte OK-432-stimulated TNF-alpha secretion. Direct blockage of the beta(2)-integrin (CD18) receptor by anti-CD18 antibody was also unable to prevent the stimulating effects of OK-432 in human monocytes. On the other hand, Syk phosphorylation is elevated upon adherence of monocytes and this is further increased by OK-432 stimulation, as shown by Western blot. The Fc-receptor was also ruled out as a main receptor of the OK-432 monocyte response. In conclusion, TNF-alpha secretion is only found in monocytes removed from blood. This TNF-alpha secretion is not mediated through the beta(1-3)-integrin receptors. OK-432 may act as a target-seeking substance whereby only monocytes adhered, e.g. to a tumour cell, become cytotoxic in part explaining why OK-432 is well suited as a cancer treatment drug.
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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/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukins,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Picibanil,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Syk kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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| pubmed:status |
MEDLINE
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| pubmed:month |
Dec
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| pubmed:issn |
1365-3083
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
66
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
684-93
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| pubmed:dateRevised |
2011-11-2
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| pubmed:meshHeading |
pubmed-meshheading:18021366-Adult,
pubmed-meshheading:18021366-Cell Adhesion,
pubmed-meshheading:18021366-Cell Differentiation,
pubmed-meshheading:18021366-Cells, Cultured,
pubmed-meshheading:18021366-Cytotoxicity, Immunologic,
pubmed-meshheading:18021366-Enzyme Inhibitors,
pubmed-meshheading:18021366-Head and Neck Neoplasms,
pubmed-meshheading:18021366-Humans,
pubmed-meshheading:18021366-Immunity, Cellular,
pubmed-meshheading:18021366-Interferon-gamma,
pubmed-meshheading:18021366-Interleukins,
pubmed-meshheading:18021366-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:18021366-Leukocytes, Mononuclear,
pubmed-meshheading:18021366-Lipopolysaccharides,
pubmed-meshheading:18021366-Lymphocyte Activation,
pubmed-meshheading:18021366-Macrophages,
pubmed-meshheading:18021366-Male,
pubmed-meshheading:18021366-Middle Aged,
pubmed-meshheading:18021366-Monocytes,
pubmed-meshheading:18021366-Picibanil,
pubmed-meshheading:18021366-Protein-Tyrosine Kinases,
pubmed-meshheading:18021366-Reference Values,
pubmed-meshheading:18021366-Tumor Necrosis Factor-alpha
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| pubmed:year |
2007
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| pubmed:articleTitle |
TNF-alpha is secreted by monocytes in transit to become macrophages, but not by peripheral blood monocytes, following OK-432 (lyophilized S. pyogenes) stimulation.
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| pubmed:affiliation |
Department of Surgical Sciences, Haukeland University Hospital, Bergen, Norway. carla.olsnes@ore.uib.no
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| pubmed:publicationType |
Journal Article
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