1. Academic Validation
  2. Overexpression of BPIFB4 Alleviates COPD Inflammatory Damage by Inhibiting M1 Macrophage Activation via the PI3K/AKT Pathway

Overexpression of BPIFB4 Alleviates COPD Inflammatory Damage by Inhibiting M1 Macrophage Activation via the PI3K/AKT Pathway

  • Lung. 2025 Jun 16;203(1):69. doi: 10.1007/s00408-025-00824-4.
Lexin Xue 1 2 Jingran Xu 3 Hui Gong 4 Zulipikaer Abudureheman 4 Ayiguli ALimu 4 Yun Chen 1 Aifang Zheng 1 Liang Gao 1 Xiuqi Lu 2 Chengxin Xie 1 Li Li 5 6 7
Affiliations

Affiliations

  • 1 Department of Respiratory and Critical Care Medicine, First People's Hospital of Kashgar, Kashgar, Xinjiang, China.
  • 2 Department of Medicine, School of Medicine, Shihezi University, Shihezi, China.
  • 3 Department of Medical College, Xinjiang Medical University, Wulumuqi, China.
  • 4 Department of Clinical Research Center of Infectious Diseases (PulmonaryTuberculosis), First People's Hospital of Kashgar, Xinjiang, China.
  • 5 Department of Respiratory and Critical Care Medicine, First People's Hospital of Kashgar, Kashgar, Xinjiang, China. lili5511@yeah.net.
  • 6 Department of Clinical Research Center of Infectious Diseases (PulmonaryTuberculosis), First People's Hospital of Kashgar, Xinjiang, China. lili5511@yeah.net.
  • 7 Department of Medical College, Xinjiang Medical University, Wulumuqi, China. lili5511@yeah.net.
Abstract

Background: Macrophage polarization is essential for inflammatory regulation in COPD. The precise role of BPI Fold-Containing Family B Member 4 (BPIFB4) in regulating the inflammatory processes underlying COPD pathogenesis remains to be fully elucidated. This investigation seeks to clarify how BPIFB4 modulates macrophage polarization by activating the phosphoinositide 3-kinase (PI3K)-AKT1 signaling pathway, thereby influencing inflammatory progression in COPD.

Methods: In a COPD mouse model induced by cigarette smoke (CS) and lipopolysaccharide (LPS) and in cigarette smoke extract (CSE)-treated THP-1 cells, BPIFB4 was overexpressed or silenced. Bronchoalveolar lavage fluid, lung tissues, and serum were collected. qPCR and western blots assessed BPIFB4 and PI3K-AKT1 pathway expression in lung tissues and THP-1 cells. Flow cytometry evaluated M1/M2 macrophage polarization, and enzyme-linked immunosorbent assay (ELISA) measured related cytokine levels.

Results: The results demonstrated how BPIFB4 gene silencing resulted in more pronounced lung tissue and functional damage compared to BPIFB4 overexpression, alongside an elevated presence of M1 macrophages and associated pro-inflammatory factors. In contrast, BPIFB4 overexpression in both COPD mice and CSE-treated THP-1 cells significantly enhanced p-AKT1 and p-PI3K levels while reducing the number of M1 macrophages. In addition, inhibition of the PI3K-AKT1 pathway reversed these effects, resulting in a marked increase in M1 macrophages and their associated cytokines.

Conclusion: BPIFB4 overexpression alleviates M1 macrophage polarization by activating the PI3K-AKT1 pathway, thereby reducing lung tissue damage and dysfunction in COPD mice.

Keywords

BPIFB4; COPD; Macrophages; PI3K-AKT1; Polarization.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-10683
    99.17%, PI3K Inhibitor