Human IL-1Ra Gene Transfer into Human Synovial Fibroblasts Is Chondroprotective

Ulf Müller-Ladner, Charles R. Roberts, Barry N. Franklin, Renate E. Gay, Paul D. Robbins, Christopher H Evans, Steffen Gay

Research output: Contribution to journalArticle

141 Citations (Scopus)

Abstract

Rheumatoid arthritis (RA) is characterized by progressive destruction of synovial cartilage. In vitro, degradation of cartilage is stimulated by IL-1, a proinflammatory cytokine, which is released from RA synovial fibroblasts (RA-SF). To determine whether gene therapy using the gene encoding the naturally occurring inhibitor of IL-1, IL-1 receptor antagonist (IL-1Ra) is feasible, IL-1Ra-transduced RA-SF were coimplanted with normal human cartilage in SCID mice. The IL-1Ra-transduced RA-SF continued to secrete IL-1Ra over a 60-day period. Cartilage that was coimplanted with RA-SF transduced with a marker gene exhibited progressive, chondrocyte-mediated cartilage degradation, whereas no such degradation was observed in cartilage that was coimplanted with RA-SF transduced with IL-1Ra. Thus, gene therapy using a retrovirus-based gene delivery system appears to be a feasible approach to effectively modifying the local synovial environment.

Original languageEnglish (US)
Pages (from-to)3492-3498
Number of pages7
JournalJournal of Immunology
Volume158
Issue number7
StatePublished - Apr 1 1997
Externally publishedYes

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Interleukin-1 Receptors
Cartilage
Rheumatoid Arthritis
Fibroblasts
Genes
Interleukin-1
Genetic Therapy
Gene Transfer Techniques
SCID Mice
Retroviridae
Chondrocytes
Cytokines

ASJC Scopus subject areas

  • Immunology

Cite this

Müller-Ladner, U., Roberts, C. R., Franklin, B. N., Gay, R. E., Robbins, P. D., Evans, C. H., & Gay, S. (1997). Human IL-1Ra Gene Transfer into Human Synovial Fibroblasts Is Chondroprotective. Journal of Immunology, 158(7), 3492-3498.

Human IL-1Ra Gene Transfer into Human Synovial Fibroblasts Is Chondroprotective. / Müller-Ladner, Ulf; Roberts, Charles R.; Franklin, Barry N.; Gay, Renate E.; Robbins, Paul D.; Evans, Christopher H; Gay, Steffen.

In: Journal of Immunology, Vol. 158, No. 7, 01.04.1997, p. 3492-3498.

Research output: Contribution to journalArticle

Müller-Ladner, U, Roberts, CR, Franklin, BN, Gay, RE, Robbins, PD, Evans, CH & Gay, S 1997, 'Human IL-1Ra Gene Transfer into Human Synovial Fibroblasts Is Chondroprotective', Journal of Immunology, vol. 158, no. 7, pp. 3492-3498.
Müller-Ladner U, Roberts CR, Franklin BN, Gay RE, Robbins PD, Evans CH et al. Human IL-1Ra Gene Transfer into Human Synovial Fibroblasts Is Chondroprotective. Journal of Immunology. 1997 Apr 1;158(7):3492-3498.
Müller-Ladner, Ulf ; Roberts, Charles R. ; Franklin, Barry N. ; Gay, Renate E. ; Robbins, Paul D. ; Evans, Christopher H ; Gay, Steffen. / Human IL-1Ra Gene Transfer into Human Synovial Fibroblasts Is Chondroprotective. In: Journal of Immunology. 1997 ; Vol. 158, No. 7. pp. 3492-3498.
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