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TNF-α-induced miR-155 regulates IL-6 signaling in rheumatoid synovial fibroblasts

Kiyoshi Migita1,2, Nozomi Iwanaga3, Yasumori Izumi3

  • 1Department of Rheumatology, Fukushima Medical University, Hikarigaoka 1, Fukushima, 960-1295, Japan. migita@fmu.ac.jp.

BMC Research Notes
|August 16, 2017
PubMed
Abstract

Insights

MicroRNAs (miRNAs) regulate inflammation. In rheumatoid arthritis, tumor necrosis factor-α induces miR-155, which then inhibits IL-6 signaling, impacting inflammatory pathways.

Area of Science:

  • Molecular Biology
  • Immunology
  • Rheumatology

Background:

  • MicroRNAs (miRNAs) are key regulators of inflammatory mediators.
  • Understanding miRNA roles in the rheumatoid cytokine network is crucial for RA pathogenesis.

Purpose of the Study:

  • To investigate the function of specific microRNAs in rheumatoid synovial fibroblasts (RASFs).
  • To elucidate the role of miR-155 in the context of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) signaling in RA.

Main Methods:

  • Analyzed miRNA expression in RASFs using miRNA array-based screening.
  • Investigated miR-155 function via transfection in RASFs.
  • Quantified miR-155 levels using real-time PCR.

Main Results:

  • miR-155-5p was significantly upregulated by TNF-α in RASFs in a time- and dose-dependent manner.
  • IL-6 stimulation did not alter miR-155 expression.
  • Overexpression of miR-155 in RASFs reduced JAK2/STAT3 phosphorylation in IL-6-treated cells.

Conclusions:

  • TNF-α modulates miRNA expression in RASFs.
  • miR-155, induced by TNF-α, inhibits IL-6-mediated JAK2/STAT3 activation.
  • miR-155 plays a role in cross-regulating TNF-α and IL-6 inflammatory pathways in rheumatoid arthritis (RA).
Keywords:
CytokinesInterleukin-6MicroRNAsRheumatoid arthritisSynovial fibroblastsTumor necrosis factor-α

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