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Updated: Jun 22, 2026
Macrophage Differentiation and Polarization into an M2-Like Phenotype using a Human Monocyte-Like THP-1 Leukemia Cell Line
Published on: August 2, 2021
Unlike PPARgamma, PPARalpha or PPARbeta/delta activation does not promote human monocyte differentiation toward
Mohamed Amine Bouhlel1, John Brozek, Bruno Derudas
1Univ Lille Nord de France, F-59000 Lille, France.
Abstract:
Macrophages adapt their response to micro-environmental signals. While Th1 cytokines promote pro-inflammatory M1 macrophages, Th2 cytokines promote an "alternative" anti-inflammatory M2 macrophage phenotype. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors expressed in macrophages where they control the inflammatory response. It has been shown that PPARgamma promotes the differentiation of monocytes into anti-inflammatory M2 macrophages in humans and mice, while a role for PPARbeta/delta in this process has been reported only in mice and no data are available for PPARalpha. Here, we show that in contrast to PPARgamma, expression of PPARalpha and PPARbeta/delta overall does not correlate with the expression of M2 markers in human atherosclerotic lesions, whereas a positive correlation with genes of lipid metabolism exists. Moreover, unlike PPARgamma, PPARalpha or PPARbeta/delta activation does not influence human monocyte differentiation into M2 macrophages in vitro. Thus, PPARalpha and PPARbeta/delta do not appear to modulate the alternative differentiation of human macrophages.
Insights
Peroxisome proliferator-activated receptors (PPARs) influence macrophage responses. PPARalpha and PPARbeta/delta do not promote anti-inflammatory M2 macrophage differentiation in humans, unlike PPARgamma.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Macrophages exhibit plasticity, with Th1 cytokines inducing pro-inflammatory M1 phenotypes and Th2 cytokines inducing anti-inflammatory M2 phenotypes.
- Peroxisome proliferator-activated receptors (PPARs) are transcription factors crucial for regulating macrophage inflammatory responses.
- PPARgamma is known to promote M2 macrophage differentiation in humans and mice, while PPARbeta/delta's role is established only in mice, and PPARalpha's role in this context is unexplored.
Purpose of the Study:
- To investigate the role of PPARalpha and PPARbeta/delta in the alternative (M2) differentiation of human macrophages.
- To determine if PPARalpha and PPARbeta/delta expression correlates with M2 markers in human atherosclerotic lesions.
- To assess the effect of PPARalpha and PPARbeta/delta activation on human monocyte differentiation in vitro.
Main Methods:
- Analysis of PPARalpha, PPARbeta/delta, and M2 marker expression in human atherosclerotic lesions.
- In vitro experiments activating PPARalpha and PPARbeta/delta in human monocytes.
- Assessment of macrophage phenotype following PPAR activation.
Main Results:
- PPARalpha and PPARbeta/delta expression did not correlate with M2 markers in human atherosclerotic lesions.
- A positive correlation was observed between PPARalpha/beta/delta expression and genes involved in lipid metabolism.
- Activation of PPARalpha or PPARbeta/delta did not alter human monocyte differentiation into M2 macrophages in vitro.
Conclusions:
- PPARalpha and PPARbeta/delta do not appear to modulate the alternative differentiation of human macrophages.
- Unlike PPARgamma, PPARalpha and PPARbeta/delta do not play a significant role in promoting M2 macrophage phenotypes in humans.
- The findings highlight differential roles of PPAR isoforms in human macrophage polarization.
