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Updated: May 5, 2026
Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
Dehydroandrographolide facilitates M2 macrophage polarization by downregulating DUSP3 to inhibit sepsis-associated
Yanyan Shao1, Weihao Yu1, Hailun Cai1
1Department of Pediatrics, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou City, China.
Background:
Sepsis is perceived as lethal tissue damage and significantly increases mortality in combination with acute kidney injury (AKI). M2 macrophages play important roles in the secretion of anti-inflammatory and tissue repair mediators. We aimed to study the role of Dehydroandrographolide (Deh) in sepsis-associated AKI in vitro and in vivo through lipopolysaccharide (LPS)-induced macrophages model and cecal ligation and puncture-induced AKI mice model, and to reveal the mechanism related to M2 macrophage polarization.
Methods:
Enzyme-linked immunosorbent assay kits were used to assess the levels of inflammatory factors. Expression of markers related to M1 macrophages and M2 macrophages were analyzed. Additionally, dual specificity phosphatase 3 (DUSP3) expression was tested. Cell apoptosis was evaluated by flow cytometry analysis and terminal-deoxynucleotidyl transferase-mediated nick end labeling staining. Moreover, renal histological assessment was performed by using hematoxylin and eosin staining.
Results:
Deh reduced inflammation of THP-1-derived macrophages exposed to LPS. Besides, Deh induced the polarization of M1 macrophages to M2 and downregulated DUSP3 expression in THP-1-derived macrophages under LPS conditions. Further, DUSP3 overexpression reversed the impacts of Deh on the inflammation and M2 macrophages polarization of THP-1-derived macrophages stimulated by LPS. Additionally, human proximal tubular epithelial cells (HK-2) in the condition medium from DUSP3-overexpressed THP-1-derived macrophages treated with LPS and Deh displayed decreased viability and increased apoptosis and inflammation. The in vivo results suggested that Deh improved the renal function, ameliorated pathological injury, induced the polarization of M1 macrophages to M2, suppressed inflammation and apoptosis, and downregulated DUSP3 expression in sepsis-induced mice.
Conclusion:
Deh facilitated M2 macrophage polarization by downregulating DUSP3 to inhibit septic AKI.
Insights
Dehydroandrographolide (Deh) combats sepsis-induced acute kidney injury (AKI) by promoting M2 macrophage polarization. This action, achieved by downregulating DUSP3, reduces inflammation and protects kidney function in sepsis models.
Area of Science:
- Immunology
- Nephrology
- Pharmacology
Background:
- Sepsis significantly elevates mortality, especially when combined with acute kidney injury (AKI).
- M2 macrophages are crucial for secreting anti-inflammatory and tissue repair mediators.
- Understanding Dehydroandrographolide's (Deh) role in sepsis-associated AKI is vital for therapeutic development.
Purpose of the Study:
- To investigate the therapeutic potential of Dehydroandrographolide (Deh) in sepsis-associated AKI.
- To elucidate the mechanism by which Deh influences M2 macrophage polarization in sepsis.
- To assess Deh's effects both in vitro using lipopolysaccharide (LPS)-induced macrophages and in vivo using a cecal ligation and puncture (CLP)-induced AKI mouse model.
Main Methods:
- Assessed inflammatory factor levels using ELISA kits.
- Analyzed M1 and M2 macrophage marker expression.
- Quantified dual specificity phosphatase 3 (DUSP3) expression.
- Evaluated cell apoptosis via flow cytometry and TUNEL staining.
- Performed renal histological assessment using H&E staining.
Main Results:
- Deh reduced LPS-induced inflammation in macrophages and promoted M1 to M2 polarization by downregulating DUSP3.
- DUSP3 overexpression reversed Deh's anti-inflammatory and M2 polarization effects.
- In vivo, Deh improved renal function, reduced pathological injury, suppressed inflammation and apoptosis, and downregulated DUSP3 in sepsis-induced mice.
Conclusions:
- Dehydroandrographolide (Deh) effectively mitigates sepsis-associated AKI.
- Deh facilitates M2 macrophage polarization through DUSP3 downregulation.
- Targeting DUSP3 with Deh presents a promising therapeutic strategy for septic AKI.
