Upregulated microRNA-155 expression in peripheral blood mononuclear cells and fibroblast-like synoviocytes in rheumatoid arthritis

Clin Dev Immunol. 2013:2013:296139. doi: 10.1155/2013/296139. Epub 2013 Sep 17.

Abstract

Objective: This study was to screen for the miRNAs differently expressed in peripheral blood mononuclear cells (PBMC) of RA, to further identify the expression of miR-155 in RA PBMC and fibroblast-like synoviocytes (FLS), and to evaluate the function of miR-155 in RA-FLS.

Methods: Microarray was used to screen for differentially expressed miRNAs in RA PBMC. miR-155 expression in PBMC and FLS of RA were identified by real-time PCR. Enforced overexpression and downexpression of miR-155 were used to investigate the function of miR-155 in RA-FLS. Expression of IKBKE which was previously identified as the actual target of miR-155 was examined by Western blot and real-time PCR in RA-FLS.

Results: miR-155 levels were increased in both PBMC and FLS of RA and could be induced by TNF- α . Upregulation of miR-155 decreased MMP-3 levels and suppressed proliferation and invasion of RA-FLS. Inverse relationship between the expressions of miR-155 and the MMPs production-related protein IKBKE was found.

Conclusion: An inflammatory milieu may alter miRNA expression profiles in rheumatoid arthritis. miR-155 is upregulated in RA-FLS, and it may be a protective factor against the inflammatory effect in part by attenuating expression of IKBKE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoptosis / genetics
  • Arthritis, Rheumatoid / genetics*
  • Case-Control Studies
  • Cell Proliferation
  • Female
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation* / drug effects
  • Humans
  • I-kappa B Kinase / genetics
  • I-kappa B Kinase / metabolism
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • Matrix Metalloproteinase 3 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Reproducibility of Results
  • Synovial Membrane / cytology*
  • Transforming Growth Factor beta / biosynthesis
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology
  • Up-Regulation
  • Young Adult

Substances

  • MIRN155 microRNA, human
  • MicroRNAs
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • I-kappa B Kinase
  • IKBKE protein, human
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 9