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Journal Article Epublish 9 citations

PubMed: 39953606 DOI: 10.1186/s40104-025-01151-7

Bovine milk-derived extracellular vesicles reduce oxidative stress and ferroptosis induced by Klebsiella pneumoniae in bovine mammary epithelial cells.

J Anim Sci Biotechnol 16(1):24

Authors: Bingchun Liang, Yindi Xiong, Eduardo R Cobo, John Kastelic, Xiaofang Tong, Bo Han, Jian Gao

Affiliations

  • Department of Clinical Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Yuanmingyuan West Road, Beijing, 100193, China.
  • Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, T2N 4N1, Canada.
  • Department of Clinical Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Yuanmingyuan West Road, Beijing, 100193, China.
  • Department of Clinical Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Yuanmingyuan West Road, Beijing, 100193, China.

Abstract

BACKGROUND

Ferroptosis is characterized by increased production of reactive oxygen species (ROS) and membrane lipid peroxidation that can exacerbate inflammatory damage. Extracellular vesicles (EVs) isolated from bovine milk have many biological functions, including antioxidant properties. However, the role of EVs on Klebsiella pneumoniae-induced ferroptosis and oxidative stress in bovine mammary epithelial cells (bMECs) and murine mammary tissue is unclear. In this study, EVs were isolated from bovine colostrum, mature milk and clinical mastitis milk (defined as C-EVs, M-EVs and CM-EVs, respectively) and assessed by transmission electron microscopy, Western blot and transcriptome sequencing. Effects of EVs on K. pneumoniae-induced ferroptosis and oxidative stress in bMECs were evaluated with immunofluorescence and Western blot.

RESULTS

In bMECs, infection with K. pneumoniae induced oxidative stress, decreasing protein expression of Nrf2, Keap1 and HO-1 plus SOD activity, and increasing ROS concentrations. However, protein expression of GPX4, ACSL4 and S100A4 in bMECs, all factors that regulate ferroptosis, was downregulated by K. pneumoniae. Furthermore, this bacterium compromised tight junctions in murine mammary tissue, with low expression of ZO-1 and Occludin, whereas protein expression of Nrf2 and GPX4 was also decreased in mammary tissue. Adding C-EVs, M-EVs or CM-EVs reduced oxidative stress and ferroptosis in K. pneumoniae-infected bMECs in vitro and murine mammary tissues in vivo.

CONCLUSION

In conclusion, all 3 sources of milk-derived EVs alleviated oxidative stress and ferroptosis in K. pneumoniae-infected bMECs and mammary tissues.

MeSH

Cells, Extracellular Vesicles, Milk, Epithelial Cells, Stress, Physiological, Ferroptosis, Oxidative Stress, Breast, Klebsiella, Tissues, Klebsiella Pneumoniae

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