Basic-helix-loop-helix transcription factor DEC2 constitutes negative feedback loop in IFN-β-mediated inflammatory

Tadaatsu Imaizumi1, Fuyuki Sato, Hiroshi Tanaka

  • 1Department of Vascular Biology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan. timaizum@cc.hirosaki-u.ac.jp

Immunology Letters
|December 7, 2010
PubMed

Insights

Differentiated embryo-chondrocyte 2 (DEC2) regulates kidney inflammation. Its expression, triggered by double-stranded RNA, acts as a negative feedback mechanism for inflammatory responses in human mesangial cells.

Area of Science:

  • Immunology
  • Molecular Biology
  • Nephrology

Background:

  • Differentiated embryo-chondrocyte 2 (DEC2) is a transcriptional factor regulating gene expression.
  • DEC2's role in kidney inflammatory responses is not fully understood.

Purpose of the Study:

  • To investigate the role of DEC2 in human mesangial cells during inflammatory stimulation.
  • To elucidate the regulatory pathway involving DEC2, double-stranded RNA, and inflammatory mediators.

Main Methods:

  • Cultured human mesangial cells were treated with polyinosinic-polycytidylic acid (poly IC).
  • RNA interference was used to knockdown DEC2 and Toll-like receptor 3 (TLR3).
  • Expression levels of IFN-β, RIG-I, and CCL5 were measured.

Main Results:

  • Poly IC treatment induced DEC2 expression in human mesangial cells.
  • Knockdown of DEC2 enhanced poly IC-induced expression of IFN-β, RIG-I, and CCL5.
  • Knockdown of TLR3 abolished poly IC-induced DEC2 expression.

Conclusions:

  • DEC2 expression is induced by double-stranded RNA via TLR3 in human mesangial cells.
  • DEC2 acts as a negative feedback regulator of the IFN-β/RIG-I/CCL5 inflammatory pathway in the glomerulus.
  • DEC2 may play a role in controlling chronic kidney inflammation.

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