Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1990-8-30
pubmed:abstractText
Interferon-gamma (IFN) is produced by lymphocytes in areas of inflammation and connective tissue destruction. IFN inhibits collagen and DNA synthesis in cultured rat long bones and osteoblastic ROS 17/2.8 cells, suggesting that the periarticular loss of bone that occurs in inflammatory joint diseases may be due to IFN inhibition of bone formation. Since serum levels of bone gla protein (BGP) have been correlated with the bone formation rate, we studied the effect of IFN on production of this osteoblast-specific protein and steady state BGP messenger RNA (mRNA) levels in ROS 17/2.8 cells. RIA of BGP was done using an antibody raised against rat BGP peptide. BGP synthesis was stimulated with 10(-8) M 1,25-dihydroxyvitamin D3 24 h before and continuously after addition of recombinant rat IFN. IFN (100 U/ml) inhibited BGP secretion 52%, 78%, and 70% in the first, second, and third 24 h periods after IFN treatment, compared to control cells cultured with 1,25-dihydroxyvitamin D3 alone. The ED50 for IFN inhibition of BGP production was 3.3 U/ml (0.29 nM). Pulse labeling with [14C]leucine or [3H]proline during the last 4 h of culture revealed that IFN (3-100 U/ml) did not inhibit total protein secretion into the medium. The percent inhibition of BGP production by IFN was independent of media serum concentration or cell density. IFN (100 U/ml) decreased the steady state level of BGP mRNA as measured by Northern analysis using an oligomeric probe for rat BGP. The decrease in hybridization signal for BGP mRNA was detectable by 1 h after IFN exposure and continued to decline at 6 and 24 h. Treatment with cycloheximide (5 micrograms/ml) blocked the inhibitory effect of IFN on steady state levels of BGP mRNA. These results suggest that IFN may inhibit bone formation by selective inhibition of osteoblast matrix protein production. The mechanism of IFN inhibition of BGP production is, at least in part, pretranslational.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
127
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
588-94
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:2115429-Amino Acid Sequence, pubmed-meshheading:2115429-Animals, pubmed-meshheading:2115429-Base Sequence, pubmed-meshheading:2115429-Blotting, Northern, pubmed-meshheading:2115429-Calcitriol, pubmed-meshheading:2115429-Culture Media, pubmed-meshheading:2115429-Cycloheximide, pubmed-meshheading:2115429-Drug Synergism, pubmed-meshheading:2115429-Interferon-gamma, pubmed-meshheading:2115429-Kinetics, pubmed-meshheading:2115429-Molecular Sequence Data, pubmed-meshheading:2115429-Neoplasm Proteins, pubmed-meshheading:2115429-Oligonucleotide Probes, pubmed-meshheading:2115429-Oligopeptides, pubmed-meshheading:2115429-Osteocalcin, pubmed-meshheading:2115429-Osteosarcoma, pubmed-meshheading:2115429-RNA, Messenger, pubmed-meshheading:2115429-Rats, pubmed-meshheading:2115429-Recombinant Proteins, pubmed-meshheading:2115429-Transcription, Genetic, pubmed-meshheading:2115429-Tumor Cells, Cultured
pubmed:year
1990
pubmed:articleTitle
Interferon-gamma inhibits 1,25-dihydroxyvitamin D3-stimulated synthesis of bone GLA protein in rat osteosarcoma cells by a pretranslational mechanism.
pubmed:affiliation
Department of Medicine, Veterans Administration Medical Center, Atlanta, Georgia 30033.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't