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Updated: Sep 27, 2025
Macrophage Differentiation and Polarization into an M2-Like Phenotype using a Human Monocyte-Like THP-1 Leukemia Cell Line
Published on: August 2, 2021
Protective effect of growth differentiation factor 15 in sepsis by regulating macrophage polarization and its
1Department of Emergency Medicine, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Abstract:
This study aims to investigate the protective effect of growth differentiation factor 15 (GDF15) in sepsis by regulating macrophage polarization and its mechanism. The mouse macrophages were cultured and treated with lipopolysaccharide (LPS), and some cells were intervened with GDF15 and LY294002. The proinflammatory activated (M1) macrophages and the anti-inflammatory activated (M2) macrophages were measured and observed, and the messenger RNA expression levels of their biomarkers, phosphatidylinositol 3-kinase (PI3K), and protein kinase B (Akt) were detected. The survival rate, cardiac function, and histopathological sections were observed. In the LPS group, after GDF15 intervention, the percentage of M1 macrophages decreased and M2 macrophages increased, the infiltration of monocytes/macrophages into the heart was inhibited, systemic and cardiac inflammation was reduced, and the survival time of the mice was prolonged. GDF15 regulated macrophage polarization and played an anti-inflammatory role by activating the phosphorylation of the PI3K/Akt signaling pathway. In patients with sepsis, the serum GDF15 level increased and was closely related to the severity of the sepsis and the 28-day mortality rate and could be used as a prognostic marker of sepsis. GDF15 regulates macrophage polarization through activating the PI3K/Akt signaling pathway and has a protective effect on survival and the cardiac function of patients with sepsis and sepsis mouse models. The increase in serum GDF15 level is closely related to severity and mortality in patients with sepsis and is therefore a prognostic marker of sepsis.
Insights
Growth Differentiation Factor 15 (GDF15) protects against sepsis by shifting macrophage polarization towards an anti-inflammatory state via the PI3K/Akt pathway. Elevated serum GDF15 levels in sepsis patients indicate severity and predict mortality.
Area of Science:
- Biomedical research
- Immunology
- Sepsis pathophysiology
Background:
- Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection.
- Macrophage polarization plays a critical role in sepsis progression and outcomes.
- Growth Differentiation Factor 15 (GDF15) is a stress-induced cytokine with potential immunomodulatory functions.
Purpose of the Study:
- To investigate the protective effects of GDF15 in sepsis.
- To elucidate the mechanism of GDF15 in regulating macrophage polarization.
- To assess GDF15 as a prognostic marker for sepsis severity and mortality.
Main Methods:
- Primary mouse macrophages were stimulated with lipopolysaccharide (LPS) and treated with GDF15 and PI3K inhibitor LY294002.
- Macrophage polarization (M1/M2), mRNA expression of key signaling molecules (PI3K, Akt), survival rates, cardiac function, and histopathology were analyzed.
- Serum GDF15 levels were measured in sepsis patients and correlated with clinical severity and mortality.
Main Results:
- GDF15 treatment reversed LPS-induced M1 macrophage polarization to M2, reducing cardiac inflammation and improving survival in mice.
- GDF15 activated the PI3K/Akt signaling pathway, mediating its anti-inflammatory and protective effects.
- Increased serum GDF15 levels in sepsis patients correlated significantly with disease severity and 28-day mortality.
Conclusions:
- GDF15 exerts protective effects in sepsis by promoting M2 macrophage polarization through the PI3K/Akt pathway.
- GDF15 demonstrates therapeutic potential for sepsis and serves as a valuable prognostic biomarker for disease severity and patient outcomes.
