Abstract
In this report, we present data showing that a recombinant adenoviral vector (Ad.RSVIL-1ra) containing the cDNA for human interleukin-1 receptor antagonist protein (IL-1ra) can genetically modify synoviocytes both in vitro and in vivo. Human synoviocytes infected with Ad.RSVIL-1ra in vitro expressed and secreted high levels of human IL-1ra that were detected by ELISA of tissue culture supernatants. New Zealand White rabbits that received intra-articular injections of Ad.RSVIL-1ra expressed transgenic IL-1ra in synoviocytes, and secretion was detected for at least 4 weeks post-infection. Further, biological activity of the transgenic IL-1ra was demonstrated by its ability to inhibit IL-1-induced prostaglandin E2 (PGE2) synthesis in vitro and IL-1-induced glycosaminoglycan (GAG) degradation in vivo. These data demonstrate that recombinant adenoviral vectors can mediate the intra-articular expression of anti-inflammatory proteins and may be a reasonable method to deliver therapeutically relevant proteins for the regional treatment of synovial inflammation.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Adenoviridae / genetics*
-
Animals
-
Anti-Inflammatory Agents / pharmacology
-
Antisense Elements (Genetics)
-
Blotting, Southern
-
Cell Line, Transformed / virology
-
Cells, Cultured / virology
-
DNA / analysis
-
DNA / chemistry
-
DNA, Complementary / chemistry
-
DNA, Complementary / genetics
-
Dinoprostone / antagonists & inhibitors
-
Dinoprostone / biosynthesis
-
Enzyme-Linked Immunosorbent Assay
-
Genetic Vectors / chemistry*
-
Genetic Vectors / genetics*
-
Humans
-
Interleukin 1 Receptor Antagonist Protein
-
Interleukin-1 / pharmacology
-
Knee Joint
-
Rabbits
-
Receptors, Interleukin-1 / antagonists & inhibitors*
-
Recombinant Proteins / pharmacology
-
Sialoglycoproteins / genetics*
-
Sialoglycoproteins / metabolism
-
Sialoglycoproteins / pharmacology
-
Synovial Membrane / cytology
-
Synovial Membrane / drug effects*
-
Synovial Membrane / virology*
-
Therapeutic Irrigation
-
Time Factors
-
Transduction, Genetic
Substances
-
Anti-Inflammatory Agents
-
Antisense Elements (Genetics)
-
DNA, Complementary
-
IL1RN protein, human
-
Interleukin 1 Receptor Antagonist Protein
-
Interleukin-1
-
Receptors, Interleukin-1
-
Recombinant Proteins
-
Sialoglycoproteins
-
DNA
-
Dinoprostone