MEF2C mediates the activation induced cell death (AICD) of macrophages

Cell Res. 2006 Jun;16(6):559-65. doi: 10.1038/sj.cr.7310073.

Abstract

Activation-induced cell death (AICD) of immune cells is widely believed to be crucial for the regulation of immune responses. Although macrophage apoptosis has been observed under a variety of pathological conditions, questions as to whether there is AICD of macrophages and how macrophage life span is regulated have not been well addressed. AICD in macrophages requires two signals. One is cell activation triggered by LPS or other bacterial components. The other is an event that exists in AICD-susceptible (primed) but not unsusceptible (resting) macrophages. Here we show that RAW264.7 cell is susceptible to LPS stimulation when it is primed with Salmonella typhimurium, type 5 adenovirus (Ad5) or IFN-gamma. We found that the stability of the transcription factor MEF2C is increased in primed RAW264.7 cell. Transfection of a dominant negative form of MEF2C protects primed macrophage from cell death triggered by LPS. Our data demonstrate that the increase of MEF2C protein stability is a key factor in the AICD of macrophage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / physiology
  • Animals
  • Cell Death*
  • Cell Line
  • Interferon-gamma / pharmacology
  • Lipopolysaccharides / pharmacology
  • MEF2 Transcription Factors
  • Macrophage Activation*
  • Macrophages, Peritoneal / immunology*
  • Macrophages, Peritoneal / microbiology
  • Macrophages, Peritoneal / virology
  • Mice
  • Mutation
  • Myogenic Regulatory Factors / genetics
  • Myogenic Regulatory Factors / physiology*
  • Salmonella typhimurium / physiology

Substances

  • Lipopolysaccharides
  • MEF2 Transcription Factors
  • Mef2c protein, mouse
  • Myogenic Regulatory Factors
  • Interferon-gamma