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Updated: Nov 2, 2025

Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells
Published on: February 21, 2018
A PGE2-MEF2A axis enables context-dependent control of inflammatory gene expression
Francesco Cilenti1, Giulia Barbiera2, Nicoletta Caronni2
1Vita-Salute San Raffaele University, Milan, Italy; San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), Milan, Italy; Genomics of the Innate Immune System Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Prostaglandin E2 (PGE2) antagonizes inflammatory gene expression by targeting MEF2A enhancers in macrophages. This mechanism is crucial for regulating immune responses and preventing tissue damage, impacting infectious diseases and cancer.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Immune homeostasis requires precise control of inflammatory gene expression.
- Prostaglandin E2 (PGE2) is a key modulator of macrophage activation, but its precise mechanisms are not fully understood.
Purpose of the Study:
- To investigate the genomic mechanisms by which PGE2 antagonizes lipopolysaccharide (LPS)-induced inflammatory gene expression in macrophages.
Main Methods:
- Genomic analysis of LPS-induced genes antagonized by PGE2.
- Chromatin organization assessment in unstimulated and stimulated macrophages.
- Myocyte enhancer factor 2A (MEF2A) deletion and its effect on gene expression.
- Analysis of ERK5 activation in response to LPS and PGE2.
Main Results:
- PGE2 targets inflammatory gene enhancers with pre-existing poorly permissive chromatin and MEF2A binding.
- MEF2A deletion mimicked PGE2 effects, inhibiting type I interferon (IFN I) induction.
- PGE2 interfered with LPS-induced ERK5 activation, a MEF2 transcriptional partner.
Conclusions:
- A transcriptional circuit involving MEF2A and ERK5 mediates IFN I induction, modulated by PGE2.
- This highlights cellular plasticity in response to environmental cues.
- Uncovered mechanisms have implications for infectious diseases and cancer therapy.
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