Storm Jasmyne A, Lu Jueqin, Obtial Mon Francis, Wijenayake Sanoji
Department of Biology, Richardson College for the Environment and Science Complex, The University of Winnipeg, Winnipeg, Manitoba, Canada.
Department of Biology, Richardson College for the Environment and Science Complex, The University of Winnipeg, Winnipeg, Manitoba, Canada.
Cell Stress Chaperones. 2025 Jul;30(4):100088. doi: 10.1016/j.cstres.2025.100088. Epub 2025 Jun 26.
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.
源自牛奶的细胞外囊泡（MEVs）可对抗外周细胞和组织中的急性和慢性促炎反应。然而，MEVs在中枢神经系统中的生物学功能仍有待探索。我们研究了MEVs是否能激活极化的人小胶质细胞中的热休克反应（HSR）。MEVs从未经巴氏杀菌的人类供体母乳中分离出来（n = 12名匿名捐赠者）。用人小胶质细胞克隆3细胞用10 ng/mL干扰素-γ预处理以诱导极化，一部分细胞补充200 μg的MEVs。在MEV处理后6小时、12小时和24小时，使用定量逆转录聚合酶链反应和western免疫印迹分析热休克因子1（HSF1）和候选热休克蛋白（Hsp70、Hsp90、Hsp40、Hsp27）的丰度。我们发现，与稳态细胞相比，MEV处理可促进极化小胶质细胞中的HSR。此外，MEVs延长了极化小胶质细胞中HSR的持续时间，发挥了强大且持续的促生存益处。
