Linked Life Data

1846871

Source:http://linkedlifedata.com/resource/pubmed/id/1846871

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1991-3-14
pubmed:abstractText
Glucocorticoids play an important role in the therapy of arthritic diseases. We sought, firstly, to identify, characterize and localize glucocorticoid receptors (GR) in normal human chondrocytes and, secondly, to determine whether glucocorticoid suppression of human recombinant interleukin-1 beta (rhIL-1 beta)-stimulated metalloproteases (MPs) synthesis by chondrocytes requires GR occupancy. Radioligand binding studies with cultured chondrocytes revealed the presence of high affinity-low capacity [3H]dexamethasone (DEX) binding sites with the following kinetic parameters: Kd = 12.5 +/- 1.4 nmol/L, Nmax = 57,560 +/- 3,960 sites per cell. Competition studies indicated that the DEX binding site was glucocorticoid specific and the competitive hierarchy established was: DEX greater than RU-26988 greater than RU-486 greater than cortisol greater than progesterone much greater than testosterone greater than estradiol-17 beta. Immunocytochemical studies using a specific anti-human GR antiserum identified immunoreactive material primarily in the cytoplasm with cells cultured in the absence of glucocorticoids. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis-Western immunoblotting analysis of chondrocyte cytosol detected the presence of a macromolecular species comigrating with a standard protein possessing a molecular weight of 94 kilodalton. rhIL-1 beta provoked the synthesis and secretion of the MPs stromelysin and collagenase from human chondrocytes in a saturable, coordinate, and dose-dependent fashion. DEX and cortisol inhibited the cytokine-stimulated MP synthesis in similar dose-dependent fashions: DEX, IC50 for stromelysin and collagenase suppression was 1.12 X 10(-8) mol/L and 1.26 X 10(-9) mol/L, respectively and the IC50 for cortisol was 6.3 X 10(-7) mol/L and 4.9 X 10(-8) mol/L, respectively. rhIL-1 beta failed to stimulate metalloprotease synthesis and release from chondrocytes pretreated with 10 nmol/L DEX, even after 20 days of incubation. The antiglucocorticoid, RU-486 completely reversed the DEX induced suppression of MP synthesis at 10(-7) mol/L. RU-486 alone had no effect on MP synthesis. We believe there is a biochemical rationale for the therapeutic efficacy of glucocorticoid administration in the management of arthritic diseases such as osteoarthritis and rheumatoid arthritis, and cytokines such as IL-1 are likely to be involved in the increase in MP synthesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-972X
pubmed:author
pubmed:issnType
Print
pubmed:volume
72
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
316-26
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:1846871-Adolescent, pubmed-meshheading:1846871-Adult, pubmed-meshheading:1846871-Binding, Competitive, pubmed-meshheading:1846871-Blotting, Western, pubmed-meshheading:1846871-Cartilage, pubmed-meshheading:1846871-Cells, Cultured, pubmed-meshheading:1846871-Dexamethasone, pubmed-meshheading:1846871-Female, pubmed-meshheading:1846871-Humans, pubmed-meshheading:1846871-Hydrocortisone, pubmed-meshheading:1846871-Immunohistochemistry, pubmed-meshheading:1846871-Interleukin-1, pubmed-meshheading:1846871-Kinetics, pubmed-meshheading:1846871-Male, pubmed-meshheading:1846871-Matrix Metalloproteinase 3, pubmed-meshheading:1846871-Metalloendopeptidases, pubmed-meshheading:1846871-Microbial Collagenase, pubmed-meshheading:1846871-Middle Aged, pubmed-meshheading:1846871-Mifepristone, pubmed-meshheading:1846871-Molecular Weight, pubmed-meshheading:1846871-Receptors, Glucocorticoid
pubmed:year
1991
pubmed:articleTitle
Glucocorticoid receptor mediated inhibition of interleukin-1 stimulated neutral metalloprotease synthesis in normal human chondrocytes.
pubmed:affiliation
Rheumatic Disease Unit, Notre-Dame Hospital, Montréal, Québec, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't