IFN-γ and TNF-α synergistically induce microRNA-155 which regulates TAB2/IP-10 expression in human mesangial cells

Am J Nephrol. 2010;32(5):462-8. doi: 10.1159/000321365. Epub 2010 Oct 18.

Abstract

Background/aims: MicroRNAs are noncoding small RNA molecules that posttranscriptionally regulate gene expression. microRNA-155 (miR-155), one of the microRNAs, is involved in the control of various genes. However, the role of miR-155 in inflammatory responses in mesangial cells is not known. In the present study, we examined the expression of miR-155 in mesangial cells.

Methods: The expression of miR-155 in cultured normal human mesangial cells treated with interferon-γ (IFN-γ) and/or tumor-necrosis factor-α (TNF-α) was examined. The cells were transfected with miR-155 mimic, siRNA against transforming growth factor-β-activated kinase-1 (TAK1)-binding protein 2 (TAB2) or siRNA against nuclear factor-κB (NF-κB).

Results: IFN-γ and TNF-α synergistically induced the expression of miR-155. Transfection of cells with miR-155 mimic inhibited the expression of TAB2 and IFN-γ-inducible protein of 10 kDa (IP-10). The expression of IP-10 was suppressed by knockdown of TAB2. Induction of miR-155 was inhibited by RNA interference against TAB2 or NF-κB.

Conclusion: Combined stimulation with IFN-γ and TNF-α induces miR-155 via TAB2 and NF-κB. miR-155 negatively regulates TAB2, as a negative feedback system, to lower IP-10 expression. miR-155 may play a role in the regulation of inflammatory and immune reactions in the kidney.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Cells, Cultured
  • Chemokine CXCL10 / genetics*
  • Chemokine CXCL10 / metabolism
  • Drug Synergism
  • Gene Expression Regulation
  • Humans
  • Inflammation Mediators / metabolism
  • Interferon-gamma / genetics*
  • Interferon-gamma / pharmacology
  • Mesangial Cells / metabolism*
  • MicroRNAs / drug effects
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / genetics
  • Transfection
  • Tumor Necrosis Factor-alpha / genetics*
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Adaptor Proteins, Signal Transducing
  • Chemokine CXCL10
  • Inflammation Mediators
  • MIRN155 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • RNA, Messenger
  • RNA, Small Interfering
  • TAB2 protein, human
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma