MicroRNA-146a expresses in interleukin-17 producing T cells in rheumatoid arthritis patients

BMC Musculoskelet Disord. 2010 Sep 15;11:209. doi: 10.1186/1471-2474-11-209.

Abstract

Background: Interleukin (IL)-17 is an important factor in rheumatoid arthritis (RA) pathogenesis. MicroRNA (miRNA)s are a family of non coding RNAs and associated with human diseases including RA. The purpose of this study is to identify the miRNAs in the differentiation of IL-17 producing cells, and analyze their expression pattern in the peripheral blood mononuclear cells (PBMC) and synovium from RA patients.

Methods: IL-17 producing cells were expanded from CD4+T cell. MiRNA microarray was performed to identify the miRNAs in the differentiation of IL-17 producing cells. Quantitative polymerase chain reaction was performed to examine the expression patterns of the identified miRNAs in the PBMC and synovium from RA and osteoarthritis (OA) patients. Double staining combining in situ hybridization and immunohistochemistry of IL-17 was performed to analyze the expression pattern of identified miRNA in the synovium.

Results: Six miRNAs, let-7a, miR-26, miR-146a/b, miR-150, and miR-155 were significantly up regulated in the IL-17 producing T cells. The expression of miR-146a and IL-17 was higher than in PBMC in the patients with low score of Larsen grade and short disease duration. MiR-146a intensely expressed in RA synovium in comparison to OA. MiR-146a expressed intensely in the synovium with hyperplasia and high expression of IL-17 from the patients with high disease activity. Double staining revealed that miR-146a expressed in IL-17 expressing cells.

Conclusion: These results indicated that miR-146a was associated with IL-17 expression in the PBMC and synovium in RA patients. There is the possibility that miR-146a participates in the IL-17 expression.

MeSH terms

  • Aged
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / pathology
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Female
  • Gene Expression Regulation / immunology
  • Humans
  • Interleukin-17 / biosynthesis*
  • Interleukin-17 / genetics
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Male
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Middle Aged
  • Synovial Membrane / cytology
  • Synovial Membrane / immunology
  • Synovial Membrane / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology

Substances

  • Interleukin-17
  • MicroRNAs
  • Mirn146 microRNA, mouse