Bovine milk exosomes contain microRNA and mRNA and are taken up by human macrophages

Abstract

We reported previously that microRNA (miRNA) are present in whey fractions of human breast milk, bovine milk, and rat milk. Moreover, we also confirmed that so many mRNA species are present in rat milk whey. These RNA were resistant to acidic conditions and to RNase, but were degraded by detergent. Thus, these RNA are likely packaged in membrane vesicles such as exosomes. However, functional extracellular circulating RNA in bodily fluids, such as blood miRNA, are present in various forms. In the current study, we used bovine raw milk and total RNA purified from exosomes (prepared by ultracentrifugation) and ultracentrifuged supernatants, and analyzed them using miRNA and mRNA microarrays to clarify which miRNA and mRNA species are present in exosomes, and which species exist in other forms. Microarray analyses revealed that most mRNA in milk whey were present in exosomes, whereas miRNA in milk whey were present in supernatant as well as exosomes. The RNA in exosomes might exert functional effects because of their stability. Therefore, we also investigated whether bovine milk-derived exosomes could affect human cells using THP-1 cells. Flow cytometry and fluorescent microscopy studies revealed that bovine milk exosomes were incorporated into differentiated THP-1 cells. These results suggest that bovine milk exosomes might have effects in human cells by containing RNA.

Survey of 800+ data sets from human tissue and body fluid reveals xenomiRs are likely artifacts

“…It has been suggested that miRNAs can be transferred from breast milk to the bloodstream (Munch et al 2013;Baier et al 2014;Izumi et al 2015), although these results have also been contested (Laubier et al 2015;Title et al 2015).…”

Biocompatibility of highly purified bovine milk‐derived extracellular vesicles

“…Similarly, mEVs from bovine milk were isolated and characterized [13]. Our group demonstrated that bovine mEV contains mRNA and miRNA [14]; thus, mEVs may deliver these RNAs to recipient cells [15]. …”

Transdermal delivery of bovine milk vesicles in patients with multiple sclerosis: A novel strategy to induce MOG-specific tolerance

“…In the second scenario, excessive presentation of BTN peptides via dermal and epidermal DCs in the absence of pro-inflammatory signals (IL-12, IL-6, and TNF-a) or co-stimulatory molecules (CD80 and CD86) may lead to T cell anergy (state of unresponsiveness to antigen) after TCR (T cell receptor) stimulation [9]. Simultaneously, extensive incorporation of membrane-bound BTN into neighbor cells' membrane (both non-immune and immune cells) is the other possible mechanism by which BTN-bearing vesicles may contribute to T cell anergy [28][29][30][31][32][33][34].…”