Ribozyme-based gene cleavage approach to chronic arthritis associated with human T cell leukemia virus type I. Induction of apoptosis in synoviocytes by ablation of HTLV-I tax protein
| Autor: | Yasufumi Kaneda, Yasuko Soejima, Ko-Ichi Kawahara, Isao Kitajima, Naohiro Hanyu, Ikuro Maruyama, Toshikazu Kubo, Ryo Yamada |
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| Rok vydání: | 1997 |
| Předmět: |
Gene Expression Regulation
Viral viruses Genetic enhancement Immunology Arthritis Apoptosis DNA Fragmentation Virus Arthritis Rheumatoid Rheumatology medicine Humans Immunology and Allergy RNA Catalytic Pharmacology (medical) RNA Messenger Gene Cells Cultured Electrophoresis Agar Gel Human T-lymphotropic virus 1 Messenger RNA biology Genes pX Synovial Membrane Gene Transfer Techniques Ribozyme Gene Products tax medicine.disease HTLV-I Infections Virology Synovial Cell biology.protein Cancer research RNA Viral Cell Division |
| Zdroj: | Arthritis & Rheumatism. 40:2118-2127 |
| ISSN: | 1529-0131 0004-3591 |
| DOI: | 10.1002/art.1780401205 |
| Popis: | Objective. To develop gene therapy for patients with human T cell leukemia virus type I (HTLV-I)-associated arthropathy (HAAP), we investigated the effects of ribozyme-mediated cleavage of HTLV-I tax/rex messenger RNA (mRNA) on synovial overgrowth. Methods. We introduced 2 hammerhead ribozymes targeted against HTLV-I tax/rex mRNA into synovial cells obtained from patients with HAAP and from patients with HTLV-I-negative rheumatoid arthritis (RA) and examined the ribozyme-mediated ablation of Tax expression. Using standard methods, we also determined the cells' ability to stop proliferating and to undergo apoptosis. Results. The ribozymes successfully cleaved tax/rex mRNA in HAAP patient synoviocytes. Both tax mRNA expression and Tax protein synthesis were inhibited significantly, resulting in inhibition of synovial cell growth and induction of apoptosis. In contrast, synovial cells from RA patients were not affected. Conclusion. In vitro results suggest that ribozyme-mediated gene therapy can inhibit the growth of HTLV-I-infected synovial cells, which is maintained by Tax protein, in HTLV-I-related diseases including HAAP. |
| Databáze: | OpenAIRE |
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