Inhibition of cartilage destruction by double gene transfer of IL-1Ra and IL-10 involves the activin pathway

Neumann, E. and Judex, M. and Kullmann, F. and Grifka, J. and Robbins, P. D. and Pap, T. and Gay, R. E. and Evans, C. H. and Gay, S. and Schoelmerich, Juergen and Mueller-Ladner, Ulf (2002) Inhibition of cartilage destruction by double gene transfer of IL-1Ra and IL-10 involves the activin pathway. GENE THERAPY, 9 (22). pp. 1508-1519. ISSN 0969-7128, 1476-5462

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Abstract

The objective of the study was to determine the effects and the molecular background of interleukin-1 receptor antagonist (IL-1Ra) and vIL-10 double gene transfer into human synovial fibroblasts from patients with rheumatoid arthritis (RA) using the SCID mouse model for cartilage erosion in RA. RA synovial fibroblasts were transduced with retro- or adenoviruses encoding IL-1Ra andlor viral IL-10 (vIL-10). SCID mice were engrafted subcutaneously with IL-1Ra and vIL-10 transduced human rheumatoid synovial fibroblasts and normal cartilage. In parallel, gene expression analysis before and after gene transfer using RNA arbitrarily primed PCR in combination with cDNA array was performed. vIL-10 and IL-lRa double gene transfer resulted in inhibition of cartilage invasion and degradation by RA synovial fibroblasts when compared with control transduced and nontransduced implants. Expression of key genes that were altered after double gene transfer were related to the activin pathway. The results demonstrate not only that virus-based gene transfer using a combination of two joint-protective genes is a feasible approach to inhibit cartilage degradation by activated RA synovial fibroblasts, but also that the underlying molecular effects include modulation of the activin pathway.

Item Type: Article
Uncontrolled Keywords: INTERLEUKIN-1 RECEPTOR ANTAGONIST; COLLAGEN-INDUCED ARTHRITIS; NECROSIS-FACTOR-ALPHA; HUMAN SYNOVIAL FIBROBLASTS; RHEUMATOID-ARTHRITIS; MESSENGER-RNA; INFLAMMATORY ARTHROPATHIES; MATRIX-METALLOPROTEINASE; EXPRESSION; PROTEIN; rheumatoid arthritis; retrovirus; adenovirus; cDNA array; RAP-PCR
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin I
Medicine > Lehrstuhl für Orthopädie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 29 Sep 2021 15:05
Last Modified: 29 Sep 2021 15:05
URI: https://pred.uni-regensburg.de/id/eprint/39718

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