Regulation of autophagy following ex vivo heating in peripheral blood mononuclear cells from young adults

• Published in: Journal of thermal biology 2020-07, Vol.91, p.102643-7, Article 102643
• Main Authors: McCormick, James J., King, Kelli E., Côté, Melissa D., McManus, Morgan K., Topshee, Serena M., Hsu, Hung-Sheng, Fujii, Naoto, Kenny, Glen P.
• Format: Article
• Language: English
• Subjects: Apoptosis; Autophagy; Body temperature; Heat; Heat shock; HSP70; HSP90; Inflammation; Leukocytes (mononuclear); Peripheral blood mononuclear cells; Phagocytosis; Temperature; Young adults
• ISSN: 0306-4565; 1879-0992
• DOI: 10.1016/j.jtherbio.2020.102643

Under conditions of extreme heat stress, the process of autophagy has previously been shown to protect human cells, but the exact body temperature at which autophagic activation occurs is largely unknown. Further, the interplay between autophagy, the heat shock response (HSR), inflammation, and apoptosis have yet to be examined together under temperature conditions representative of human internal body temperatures at rest (37 °C) or under severe heat stress conditions (41 °C). Thus, the purpose of this study was to examine threshold changes in autophagy, the HSR, inflammation, and apoptosis to increasing levels of ex vivo heat stress. Whole blood was collected from 20 young (23 ± 4 years; 10 men, 10 women) physically active participants. Peripheral blood mononuclear cells (PBMCs) were isolated immediately (baseline) and after 90-min of whole blood heating in 37, 39, and 41 °C water baths, representative of normal resting (non-heat stress) as well as moderate and severe heat stress conditions in humans, respectively. At 37 °C, increased autophagic activity was demonstrated, with no change in the HSR, and inflammation. Subsequently, responses of autophagy, the HSR, and inflammation increased with a moderate heat stress (39 °C), with further increases in only autophagy and the HSR under a severe heat stress of 41 °C. We observed no increase in apoptosis under any temperature condition. Our findings show that in human PBMCs, the autophagy and HSR systems may act cooperatively to suppress apoptotic signaling following heat stress, which may in part be mediated by an acute inflammatory response. •Exposure to physiologically relevant elevations in temperature increases autophagy.•Autophagy and heat shock protein activation may suppress apoptosis during heating.•Acute inflammation during heating may in part stimulate autophagy.