Inhibition of interleukin-1-induced effects in synoviocytes transduced with the human IL-1 receptor antagonist cDNA using an adenoviral vector.
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.
Roessler
B J
BJ
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0680, USA.
Hartman
J W
JW
Vallance
D K
DK
Latta
J M
JM
Janich
S L
SL
Davidson
B L
BL
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D016375:Antisense Elements (Genetics); D015139:Blotting, Southern; D002461:Cell Line, Transformed / Q000821:virology; D002478:Cells, Cultured / Q000821:virology; D004247:DNA / Q000032:analysis / Q000737:chemistry; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005822:Genetic Vectors / Q000737:chemistry* / Q000235:genetics*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology; D007719:Knee Joint; D011817:Rabbits; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects* / Q000821:virology*; D007507:Therapeutic Irrigation; D013997:Time Factors; D014161:Transduction, Genetic
D000893:Anti-Inflammatory Agents; D016375:Antisense Elements (Genetics); D018076:DNA, Complementary; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D004247:DNA; D015232:Dinoprostone