Bovine Milk Exosomes Affect Proliferation and Protect Macrophages against Cisplatin-Induced Cytotoxicity

ABSTRACT

Background

Exosomes are extracellular vesicles involved in intercellular communication. The objectives were to characterize bovine milk exosomes (BME) and determine its effect on RAW 264.7 macrophages.

Methods

BME were isolated using differential centrifugation and characterized by particle size and the presence of exosomal markers Alix, TSG101, and CD81. The effect of in vitro digestion and different pH on the stability of BME was investigated. The biological activity of BME in RAW 264.7 macrophages was conducted by assessing proliferation and cell cycle. Moreover, the protective effect of exosomes on cisplatin-induced cytotoxicity was evaluated.

Results

BME have an average particle size of 106.8 ± 3.4 nm and expressed Alix, TSG101, and CD81. TSG101 was detected after digestion and exposure to different pH values. Cell-cycle analysis showed that BME reduced the percentage of apoptotic cells while arresting the cells in G2/M phase accompanied by differential expression of proliferation markers p53, p21, cyclin D1, and β-catenin. Exosomes protected macrophages against cisplatin-induced cytotoxicity.

Conclusion

Our results showed for the first time the effect of BME on the proliferation of RAW 264.7 macrophages and its protective effect against chemotherapeutic drug-induced cytotoxicity. Potential effect of BME on immune system must be studied.

KEYWORDS:

• Bovine milk
• cell cycle
• exosomes
• proliferation
• RAW 264.7 macrophages

Disclosure statement

The authors declare no conflict of interest.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Additional information

Funding

This work was supported by USDA-NIFA [HATCH 1010230].