Document Detail

Signal transduction in endotoxin-stimulated synthesis of TNF-alpha and prostaglandin E2 by rat Kupffer cells. Role of extracellular calcium ions and protein kinase C.
MedLine Citation:
PMID:  1772595     Owner:  NLM     Status:  MEDLINE    
Endotoxin is a well established elicitor of cytokine production in mononuclear cells. Nevertheless, the path of signal transduction between the crucial contact of the cells with endotoxin (lipopolysaccharide) and the synthesis and release of the mediators is yet poorly understood. In particular, the involvement of Ca2+ and protein kinase C in this process is still a matter of controversy. Here, it will be demonstrated that removal of extracellular Ca2+ by EGTA does not have a significant effect on the endotoxin-stimulated production of tumor necrosis factor-alpha (TNF-alpha) and on total protein synthesis in rat Kupffer cells. However, the release of prostaglandin E2 could not be raised above the basal level under these conditions. Treatment with inhibitors of protein kinase C such as the isoquinoline derivative, H-7, or staurosporin is without influence on TNF-alpha synthesis. The depletion of protein kinase C through preincubation of rat Kupffer cells with phorbol 12-myristate 13-acetate for 24 h was also without effect on TNF-alpha production. The effectiveness of these inhibitors under the conditions used was ascertained by measurement of the O2- release from the same cell batches. Superoxide production known as protein kinase C-dependent in Kupffer cells (Dieter et al. (1986) Eur. J. Biochem. 86, 451-457) was suppressed in a dose-dependent manner by staurosporin or after prolonged pretreatment with the phorbol ester. H-7 decreased superoxide production only slightly in high doses that severely harm the Kupffer cells. Prostaglandin E2 release, although clearly protein-kinase C-dependent in phagocytosing rat Kupffer cells, is not decreased following exposure to lipopolysaccharide in the presence of protein kinase C inhibitors.
L Weinhold; A Schulze-Specking; K Decker
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biological chemistry Hoppe-Seyler     Volume:  372     ISSN:  0177-3593     ISO Abbreviation:  Biol. Chem. Hoppe-Seyler     Publication Date:  1991 Sep 
Date Detail:
Created Date:  1992-03-05     Completed Date:  1992-03-05     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8503054     Medline TA:  Biol Chem Hoppe Seyler     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  829-34     Citation Subset:  IM    
Biochemisches Institut der Universität, Freiburg i. Br.
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MeSH Terms
Alkaloids / pharmacology
Calcium / pharmacology*
Cells, Cultured
Dinoprostone / biosynthesis*
Egtazic Acid / pharmacology
Endotoxins / pharmacology*
Interferon-gamma, Recombinant / pharmacology
Isoquinolines / pharmacology
Kupffer Cells / drug effects,  physiology*
Piperazines / pharmacology
Protein Kinase C / antagonists & inhibitors,  metabolism*
Rats, Inbred Strains
Tetradecanoylphorbol Acetate / pharmacology
Tumor Necrosis Factor-alpha / biosynthesis*
Zymosan / pharmacology
Reg. No./Substance:
0/Alkaloids; 0/Endotoxins; 0/Interferon-gamma, Recombinant; 0/Isoquinolines; 0/Lipopolysaccharides; 0/Piperazines; 0/Tumor Necrosis Factor-alpha; 16561-29-8/Tetradecanoylphorbol Acetate; 363-24-6/Dinoprostone; 62996-74-1/Staurosporine; 67-42-5/Egtazic Acid; 7440-70-2/Calcium; 84477-87-2/1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; 9010-72-4/Zymosan; EC Kinase C

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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