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Published on: October 31, 2017
MEF2C mediates the activation induced cell death (AICD) of macrophages
Wenxia Fu1, Jinxue Wei, Jun Gu
1National Key Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life Science, Peking University, Beijing 100871, China.
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.
Insights
Activation-induced cell death (AICD) in macrophages is critical for immune regulation. This study reveals that increased MEF2C protein stability in primed macrophages is key to their AICD, offering new insights into macrophage lifespan control.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Activation-induced cell death (AICD) is vital for immune response regulation.
- Macrophage apoptosis occurs in pathology, but AICD and lifespan regulation remain unclear.
- AICD in macrophages requires cell activation and a priming event.
Purpose of the Study:
- To investigate if macrophages undergo AICD.
- To identify mechanisms regulating macrophage lifespan.
- To determine the role of MEF2C in macrophage AICD.
Main Methods:
- Utilized RAW264.7 macrophage cell line.
- Primed macrophages with Salmonella typhimurium, adenovirus type 5 (Ad5), or IFN-gamma.
- Assessed susceptibility to LPS-induced cell death.
- Analyzed MEF2C protein stability.
- Used dominant-negative MEF2C transfection.
Main Results:
- Primed RAW264.7 cells showed susceptibility to LPS-induced cell death.
- MEF2C protein stability increased in primed macrophages.
- Dominant-negative MEF2C protected primed macrophages from LPS-induced death.
Conclusions:
- Macrophages are susceptible to AICD when primed.
- Increased MEF2C protein stability is a critical factor in macrophage AICD.
- MEF2C plays a key role in regulating macrophage lifespan.
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