Linked Life Data

2478116

Source:http://linkedlifedata.com/resource/pubmed/id/2478116

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
84
pubmed:dateCreated
1989-11-15
pubmed:abstractText
C1-inhibitor (C1-inh) is synthesised and secreted by at least four cell types: hepatocytes, mononuclear phagocytes, fibroblasts and umbilical vein endothelial cells. The production of this protein by monocytes/macrophages and Hep G2 cells has been studied in great detail. Environmental factors alter C1-inh synthesis by these cells. A number of agents which inhibit monocyte C1-inh production (such as histamine, PGE2 C5a des arg and serum treated immune complexes) bind to membrane receptors, activate adenylate cyclase, elevate intracellular cAMP and activate cAMP-dependent protein kinase. Elevation of monocyte cAMP levels is associated with decreased C1-inh secretion by these cells and reduced C1-inh mRNA levels. These changes can be seen within 8 hours of exposure. Stimulation of monocyte C1-inh synthesis occurs after the addition of agents which induce the formation of sodium ion and calcium ion channels, activate the phosphatidyl inositol cycle and activate protein kinase C (immune-complexes, carbamylcholine and phenylephrine). Agents which act directly on protein kinase C (phorbol myristate acetate) also stimulate C1-inh synthesis. Amongst the most potent stimulators of monocyte and Hep G2 C1-inh synthesis are the interferons (Ifns) Ifn alpha, Ifn beta and Ifn gamma. These are known to bind to specific receptors on cells (Ifn alpha and beta binding to Type I Ifn receptors and Ifn-gamma binding to type II Ifn receptors). At least two mechanisms by which Ifn receptor-ligand interaction elicit their effects exist. These are: 1) binding of an activated receptor transducer/regulatory component to specific DNA sequences on Ifn sensitive genes; 2) the activation of protein kinase C and binding of its regulatory components to specific DNA sequences. Ifn alpha, beta and gamma cause a dose related increase in monocyte and Hep G2 cell C1-inh mRNA abundance and protein synthesis. Ifn-gamma is the most potent of the interferons on monocyte C1-inh synthesis. Ifn alpha and beta being less effective but equipotent. These cytokines elicit their maximum effect on monocyte C1-inh synthesis after 1-2 hours treatment. This rapid stimulation of monocyte C1-inh synthesis suggests that this increases the transcription of the C1-inh gene. After removal of Ifns from monocytes the elevated C1-inh mRNA levels subside towards control levels of expression in Ifn alpha and beta-treated cells but remain elevated in Ifn-gamma-treated monocytes. This binding suggests that Ifn-gamma alters the stability of C1-inh mRNA.(ABSTRACT TRUNCATED AT 400 WORDS)
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0301-0457
pubmed:author
pubmed:issnType
Print
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
180-92
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
Regulation of C1-inhibitor synthesis by interferons and other agents.
pubmed:affiliation
University Department of Pathology, Western Infirmary, Glasgow, U.K.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't