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Brain Behav Immun. 2019 Jan;75:251-257. doi: 10.1016/j.bbi.2018.10.001. Epub 2018 Oct 25.

Aerobic endurance training status affects lymphocyte apoptosis sensitivity by induction of molecular genetic adaptations.

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Department of Sports Medicine, Institute of Sports Sciences, Justus-Liebig-University, Giessen, Germany.
Institute of Sports Science, Department Exercise and Health, Leibniz University, Hannover, Germany.
Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany.
Center for Extracorporeal Organ Support, Department of Internal Medicine, Universitätsmedizin Rostock, Rostock, Germany.
Witten/Herdecke University, Faculty of Health/School of Medicine, Witten, Germany. Electronic address:


Apoptosis is a genetically regulated form of programmed cell death which promotes the elimination of potentially detrimental immune cells. However, exercise-associated apoptosis is thought to induce a temporarily decline of the adaptive immune competence in the early post-exercise period. The purpose of the present study was to investigate if the aerobic endurance training status affects the sensitivity of human peripheral blood lymphocytes towards different types of apoptosis inducers and secondly, if this is mediated by the modulation of apoptosis-associated proteins and microRNAs. Collected at resting conditions, isolated lymphocytes of endurance trained athletes (ET) and healthy untrained subjects were either exposed to phytohemagglutinin-L (PHA-L), hydrogen peroxide (H2O2), or dexamethasone (DEX) as apoptosis inducer. Results revealed no significant differences between ET and UT in terms of lymphocyte apoptosis immediately following isolation as determined by flow cytometry using annexin V staining. After 24 h of ex vivo cultivation, lymphocytes of ET showed a reduced sensitivity to PHA-L-induced lymphocyte apoptosis which was accompanied by a noticeably up-regulation of the prominent apoptosis inhibitor genes X-linked inhibitor of apoptosis (XIAP) and Cyclin dependent kinase inhibitor 1B (CDKN1B) as analyzed by quantitative real-time PCR. Moreover, a trend was observed for the suppression of the corresponding pro-apoptotic miR-221. Lymphocyte apoptosis in control, H2O2 and DEX treated cells was not affected by aerobic endurance training status. However, distinct molecular signatures could be identified in un-treated control samples characterized by a counterbalanced modulation of pro- and anti-apoptotic mediators in ET. The results of the current study suggest that lymphocytes adapt to repetitive endurance exercise training by promoting lymphocyte homeostasis and increasing their resistance to apoptosis. This could be based on an up-regulation of anti-apoptotic proteins and a reduction in pro-apoptotic microRNAs which together tightly regulate the genetically defined apoptotic pathways governed by the type of apoptosis stimuli. Thus, the lymphocytes of endurance-trained athletes may be primed to counteract the transient immune suppression post-exercise.


Aerobic endurance training status; Apoptosis genes; Apoptotic miRNAs; Lymphocyte apoptosis


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