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Titolo:
SIGNAL-TRANSDUCTION THROUGH CHONDROCYTE INTEGRIN RECEPTORS INDUCES MATRIX METALLOPROTEINASE SYNTHESIS AND SYNERGIZES WITH INTERLEUKIN-1
Autore:
ARNER EC; TORTORELLA MD;
Indirizzi:
DUPONT MERCK PHARMACEUT CO,INFLAMMATORY DIS RES,EXPTL STN E400-4239,BOX 80400 WILMINGTON DE 19880
Titolo Testata:
Arthritis and rheumatism
fascicolo: 9, volume: 38, anno: 1995,
pagine: 1304 - 1314
SICI:
0004-3591(1995)38:9<1304:STCIRI>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
RABBIT ARTICULAR CHONDROCYTES; ANTIGEN-INDUCED ARTHRITIS; ENDOTHELIAL-CELL GROWTH; SYNOVIAL-FLUID; RECOMBINANT INTERLEUKIN-1-BETA; FIBRONECTIN FRAGMENTS; RHEUMATOID-ARTHRITIS; HUMAN CARTILAGE; COLLAGENASE; EXPRESSION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
59
Recensione:
Indirizzi per estratti:
Citazione:
E.C. Arner e M.D. Tortorella, "SIGNAL-TRANSDUCTION THROUGH CHONDROCYTE INTEGRIN RECEPTORS INDUCES MATRIX METALLOPROTEINASE SYNTHESIS AND SYNERGIZES WITH INTERLEUKIN-1", Arthritis and rheumatism, 38(9), 1995, pp. 1304-1314

Abstract

Objective, To study the role of signal transduction via integrin receptors in the production of metalloproteinase by rabbit articular chondrocytes. Methods. Confluent, primary rabbit articular chondrocytes (RAG) were incubated for 72 hours in the presence of interleukin-l (IL-1), Arg-Gly-Asp (RGD) peptide, or a combination of IL-1 and RGD peptide,Media were analyzed for stromelysin enzymatic activity using a H-3-labeled transferrin substrate, and for stromelysin and collagenase protein by Western analysis. Gelatinase activity was analyzed by gelatin zymography. IL-l receptor antagonist (IL-1Ra) protein was used to determine the involvement of IL-1 in mediating the effects of RGD peptide, and fluorescence-activated cell sorter analysis (FAGS) was used to examine the effect of IL-l on chondrocyte integrin subunit expression. Results. RGD peptides induced chondrocyte synthesis of stromelysin, collagenase, and 92-kd gelatinase B, and increased synthesis of the constitutively expressed 72-kd gelatinase A, Further studies focusing on stromelysin demonstrated that this up-regulation was concentration dependent and that RGD peptides synergized with IL-1 in inducing stromelysin synthesis, RGD-induced stromelysin production was inhibited by the IL-1Ra in a concentration-dependent manner, indicating that induction by RGD requires binding of IL-1 to its receptor, FAGS analysis of RAC showed that IL-1 stimulation increased the expression of beta 1 and alphav integrin subunits on the chondrocyte surface. Conclusion. Our data demonstrate that signal transduction through chondrocyte integrin receptors up-regulates metalloproteinase expression and that this is likely mediated through induction of IL-1, They also suggest that the binding of adhesion molecules to their chondrocyte integrin receptors reduces the amount of IL-l required to induce stromelysin synthesis, Upregulation of chondrocyte integrin expression by IL-1 may play a role in the synergistic effects seen with a combination of IL-1 and RGD peptides, Since elevated levels of both IL-1 and adhesion molecules are present in rheumatoid arthritis and osteoarthritis synovial fluid, our datasuggest that this interaction may be important in mediating the cartilage destruction accompanying these diseases.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/09/20 alle ore 06:47:41