INTRODUCTION A bout of vigorous endurance exercise transiently activates Toll-like receptor 4 (TLR4) and reduces TLR4 protein expressed on peripheral blood mononuclear cells (PBMCs). Endurance training, on the other hand, reduces TLR4-mediated signaling and minimizes the physiological stress imposed by exercise. Less is known about what occurs in skeletal muscle regarding TLR4 regulation and signaling. Therefore, this study aimed to investigate the regulation of TLR4 expressed in different tissue types (PBMCs and skeletal muscle samples) between endurance-trained and untrained men following vigorous endurance exercise and determine the effect of training status on cytokine responses associated with TLR4 activation. METHODS Endurance-trained (n = 7) and untrained (n = 5) men cycled for 1-hr at their respiratory compensation point, with blood and skeletal muscle samples collected pre- and 3-hours post-exercise. RESULTS In response to vigorous exercise, untrained men experienced a decrease in inhibitor of κBα (IκBα) protein (suggesting IκB degradation and the activation of TLR4-associated transcription factor NF-κB) and TLR4 protein levels, along with a simultaneous increase in TLR4 mRNA expression in both skeletal muscle and PBMCs. Moreover, this exercise session led to elevated levels of circulating interleukin-6, tumor necrosis factor-α, and interleukin-1β. Collectively, these results suggest a heightened TLR4-mediated signaling pathway in untrained men. However, no changes in these targets were observed in endurance-trained men, possibly indicating a potential mechanism by which regular endurance training blunts systemic inflammation. CONCLUSIONS These findings highlight the potential of endurance training to mitigate TLR4-mediated signaling, such as systemic inflammation, and shed light on the effects of exercise on TLR4 expression in PBMCs and skeletal muscle.

中文翻译：

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训练状态影响肌肉和 PBMC TLR4 表达的调节以及全身细胞因子对剧烈耐力运动的反应。


引言 一轮剧烈的耐力运动会短暂激活 Toll 样受体 4 （TLR4） 并减少外周血单核细胞 （PBMC） 上表达的 TLR4 蛋白。另一方面，耐力训练减少了 TLR4 介导的信号传导，并最大限度地减少了运动带来的生理压力。关于骨骼肌中关于 TLR4 调节和信号传导的情况知之甚少。因此，本研究旨在探讨耐力训练和未训练男性在剧烈耐力运动后不同组织类型 （PBMC 和骨骼肌样本） 中表达 TLR4 的调节，并确定训练状态对与 TLR4 激活相关的细胞因子反应的影响。方法 耐力训练 （n = 7） 和未训练 （n = 5） 男性在呼吸补偿点骑行 1 小时，在运动前和运动后 3 小时收集血液和骨骼肌样本。结果 作为对剧烈运动的反应，未经训练的男性经历了 κBα （IκBα） 蛋白抑制剂 （表明 IκB 降解和 TLR4 相关转录因子 NF-κB 的激活）和 TLR4 蛋白水平降低，同时骨骼肌和 PBMC 中 TLR4 mRNA 表达增加。此外，该锻炼导致循环白细胞介素 6 、肿瘤坏死因子-α 和白细胞介素 1β 水平升高。总的来说，这些结果表明，未经训练的男性 TLR4 介导的信号通路增强。然而，在耐力训练的男性中没有观察到这些目标的变化，这可能表明定期耐力训练减弱全身炎症的潜在机制。 结论这些发现强调了耐力训练在减轻 TLR4 介导的信号传导（如全身炎症）方面的潜力，并阐明了运动对 PBMC 和骨骼肌中 TLR4 表达的影响。