Chemically modified ribozyme targeting TNF-α mRNA regulates TNF-α and IL-6 synthesis in synovial fibroblasts of patients with rheumatoid arthritis

Minako Takahashi, Tadao Funato, Yoko Suzuki, Hiroshi Fujii, Keiko Kumura Ishii, Mitsuo Kaku, Takeshi Sasaki

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Rheumatoid arthritis (RA) is chronic polyarthritis in which a variety of inflammatory cytokines play a role. Since tumor necrosis factor-α (TNF-α) is one of the most important cytokines in the pathogenesis of RA, we evaluated the feasibility of ribozymes as a therapeutic agent to control the inflammatory process of RA synovium. A hammerhead ribozyme against TNF-α was chemically modified to increase nuclease resistance and added to RA fibroblastlike cell cultures without using a delivery system. The cellular uptake of fluorescent-labeled ribozyme into synovial cells was found to last at least 48 hr by confocal laser scanning microscopy. The ribozyme targeting TNF-α gene inhibited both the expression of TNF-α mRNA and the secretion of TNF-α and IL-6. The cytotoxic effect by the ribozyme on synovial cells was negligible when determined by an alamar blue assay. Chemically modified ribozymes designed to suppress the TNF-α gene may be potential as a therapeutic agent for rheumatoid arthritis.

Original languageEnglish
Pages (from-to)228-236
Number of pages9
JournalJournal of Clinical Immunology
Volume22
Issue number4
DOIs
Publication statusPublished - 2002

Keywords

  • Antisense oligonucleotides
  • Rheumatoid arthritis
  • Ribozyme
  • TNF-α gene

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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