TY - JOUR
T1 - Human IL-1Ra Gene Transfer into Human Synovial Fibroblasts Is Chondroprotective
AU - Müller-Ladner, Ulf
AU - Roberts, Charles R.
AU - Franklin, Barry N.
AU - Gay, Renate E.
AU - Robbins, Paul D.
AU - Evans, Christopher H.
AU - Gay, Steffen
PY - 1997/4/1
Y1 - 1997/4/1
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.158.7.3492
DO - 10.4049/jimmunol.158.7.3492
M3 - Article
C2 - 9120311
AN - SCOPUS:0031112232
SN - 0022-1767
VL - 158
SP - 3492
EP - 3498
JO - Journal of Immunology
JF - Journal of Immunology
IS - 7
ER -