ABSTRACT
MicroRNAs (miRNA) play a key role for morphogenesis or various diseases like cancer. Small RNA, has no protein-encoding sequence, has been indentified to interfere with stability or translational ratio of mRNA. MiRNA is one of the small RNA family and has been analyzed about the synthesis, function and target genes. These researches lead exploitation of new nucleic drugs. Many researches have been reported for relationship between miRNA and rheumatoid arthritis (RA)/osteoarthritis (OA). MiR-146a and -155 were mainly reported for RA, miR-140 was mainly reported for OA including cartilage development. This article was summarized various analysis for miRNA with RA and OA.
Subject(s)
Arthritis, Rheumatoid/genetics , MicroRNAs , Animals , Arthritis, Rheumatoid/drug therapy , Cartilage/embryology , Humans , MicroRNAs/physiology , Molecular Targeted Therapy , Osteoarthritis/drug therapy , Osteoarthritis/genetics , Protein Biosynthesis , RNA Stability , RNA, Small Interfering/geneticsABSTRACT
OBJECTIVE: To clarify the glucose-6-phosphate isomerase (GPI)-specific CD4+ T cell lineage involved in GPI-induced arthritis and to investigate their pathologic and regulatory roles in the induction of the disease. METHODS: DBA/1 mice were immunized with GPI to induce arthritis. CD4+ T cells and antigen-presenting cells were cocultured with GPI, and cytokines in the supernatant were analyzed by enzyme-linked immunosorbent assay. Anti-interferon-gamma (anti-IFNgamma) monoclonal antibody (mAb), anti-interleukin-17 (anti-IL-17) mAb, or the murine IL-6 receptor (IL-6R) mAb MR16-1 was injected at different time points, and arthritis development was monitored visually. After MR16-1 was injected, percentages of Th1, Th2, Th17, and Treg cells were analyzed by flow cytometry, and CD4+ T cell proliferation was analyzed using carboxyfluorescein diacetate succinimidyl ester. RESULTS: GPI-specific CD4+ T cells were found to be differentiated to Th1 and Th17 cells, but not Th2 cells. Administration of anti-IL-17 mAb on day 7 significantly ameliorated arthritis (P < 0.01), whereas administration of anti-IFNgamma mAb exacerbated arthritis. Neither anti-IL-17 mAb nor anti-IFNgamma mAb administration on day 14 ameliorated arthritis. Administration of MR16-1 on day 0 or day 3 protected against arthritis induction, and MR16-1 administration on day 8 significantly ameliorated existing arthritis (P < 0.05). After administration of MR16-1, there was marked suppression of Th17 differentiation, without an increase in Th1, Th2, or Treg cells, and CD4+ T cell proliferation was also suppressed. CONCLUSION: IL-6 and Th17 play an essential role in GPI-induced arthritis. Since it has previously been shown that treatment with a humanized anti-IL-6R mAb has excellent effects in patients with rheumatoid arthritis (RA), we propose that the IL-6/IL-17 axis might also be involved in the generation of RA, especially in the early effector phase.
