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Published on: January 30, 2014
Human milk-derived extracellular vesicles promote the heat shock response in polarized microglia
Jasmyne A Storm1, Jueqin Lu1, Mon Francis Obtial1
1Department of Biology, Richardson College for the Environment and Science Complex, The University of Winnipeg, Winnipeg, Manitoba, Canada.
Abstract:
Milk-derived extracellular vesicles (MEVs) combat acute and chronic pro-inflammation in peripheral cells and tissues. However, the biological functions of MEVs in the central nervous system require exploration. We investigated whether MEVs activate the heat shock response (HSR) in polarized human microglia. MEVs were isolated from unpasteurized human donor milk (n=12 anonymous donors). Human microglia clone 3 cells were primed with 10 ng/mL interferon-gamma to induce polarization, and a subset of cells was supplemented with 200 µg of MEVs. The abundance of HSF1 and candidate heat shock proteins (Hsp70, Hsp90, Hsp40, Hsp27) was analyzed using quantitative reverse transcription polymerase chain reaction and western immunoblotting at 6 h, 12 h, and 24 h post-MEV treatment. We found that MEV treatment promoted the HSR in polarized microglia, compared to homeostatic cells. Furthermore, MEVs increased the duration of the HSR in polarized microglia, exerting robust and continued pro-survival benefits.
Insights
Milk-derived extracellular vesicles (MEVs) activate the heat shock response in human microglia. This activation offers significant pro-survival benefits, particularly in inflamed conditions.
Area of Science:
- Neuroscience
- Cell Biology
- Extracellular Vesicle Research
Background:
- Milk-derived extracellular vesicles (MEVs) are known to modulate peripheral inflammation.
- The role of MEVs within the central nervous system (CNS) and their impact on microglial cells remains largely unexplored.
- Microglia are key immune cells in the CNS, and their activation state influences neuroinflammation.
Purpose of the Study:
- To investigate the effect of MEVs on the heat shock response (HSR) in polarized human microglia.
- To determine if MEVs can modulate the HSR pathway in microglia, a critical CNS immune cell type.
Main Methods:
- Isolation of MEVs from unpasteurized human donor milk.
- Polarization of human microglia clone 3 cells using interferon-gamma.
- Treatment of polarized microglia with MEVs and analysis of heat shock factor 1 (HSF1) and heat shock proteins (Hsp70, Hsp90, Hsp40, Hsp27) via qPCR and Western blotting.
Main Results:
- MEV treatment significantly promoted the heat shock response in polarized microglia compared to homeostatic cells.
- MEVs were found to prolong the duration of the HSR in polarized microglia.
- MEV administration conferred robust and sustained pro-survival advantages to polarized microglia.
Conclusions:
- MEVs activate the heat shock response pathway in polarized human microglia.
- MEVs enhance the resilience and survival of microglia, suggesting a potential therapeutic role in CNS inflammatory conditions.
- Further research into MEVs' neuroprotective mechanisms is warranted.
