INDUCTION OF APOPTOSIS IN THE RHEUMATOID SYNOVIUM BY FAS LIGAND GENE-TRANSFER

Citation
K. Okamoto et al., INDUCTION OF APOPTOSIS IN THE RHEUMATOID SYNOVIUM BY FAS LIGAND GENE-TRANSFER, Gene therapy, 5(3), 1998, pp. 331-338
Citations number
39
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biothechnology & Applied Migrobiology","Genetics & Heredity",Biology,"Medicine, Research & Experimental
Journal title
ISSN journal
0969-7128
Volume
5
Issue
3
Year of publication
1998
Pages
331 - 338
Database
ISI
SICI code
0969-7128(1998)5:3<331:IOAITR>2.0.ZU;2-X
Abstract
We have recently reported that local administration of anti-Fas monocl onal antibody (MAb) in human T cell leukemia virus type 1 (HTLV-1) car rying mice improved arthritis due to the induction of apoptosis. This finding strongly indicated the beneficial therapeutic effect of Fas-me diated apoptosis in rheumatoid arthritis (RA). To establish further th e therapeutic effect of Fas-mediated apoptosis on RA taking into consi deration safety and practicality, we investigated the effect of cells transfected with human Fas ligand (hFasL) gene on proliferating human rheumatoid synovium engrafted in severe combined immunodeficiency (SCI D-RA) mice. The hFasL transfectants exhibited cytotoxic activity again st RA synoviocytes via the Fas/FasL system in vitro. Histopathological and immunohistochemical studies showed that local injection of irradi ated-hFasL transfectants eliminated synoviocytes and mononuclear cell in engrafted human rheumatoid synovium of SCID-RA mice. Furthermore, i n situ nick end labeling analysis confirmed that the cell in engrafted synovium frequently underwent apoptosis by irradiated-hFasL transfect ants. Our results clearly demonstrated that hFasL transfectants induce d apoptosis by cell-to-cell interaction via the Fas/FasL system. Thus, ex vivo gene transfer of FasL may represent a novel therapeutic strat egy for RA.