Graduate School of Life Sciences, Toyo University, Gunma 374-0193, Japan.
Endocr J. 2023 Jun 28;70(6):601-610. doi: 10.1507/endocrj.EJ22-0611. Epub 2023 Mar 11.
The skeletal muscle is an endocrine organ that produces proteins and peptides, collectively termed as myokines. The temperature of skeletal muscles varies during exercise and/or with changes in ambient temperature. However, whether myokine secretion is regulated by heat stimulation is unclear. Thus, we aimed to explore the effects of environmental heat stimulation on myokine secretion. We initially investigated the secretome of C2C12 myotubes and identified several novel heat-responsive myokines. The concentration of C-C motif chemokine ligand 5 (CCL5) dramatically decreased by 0.3-fold in response to heat stress. After 3 h heat stimulation of C2C12 cells, the expression of heat shock protein 70 was induced, and the gene expression and secretion of CCL5 was significantly attenuated in C2C12 cells. We then examined the effects of acute heat stress on serum CCL5 levels in mice and Ccl5 gene expression in skeletal muscles. Mice were maintained at 23°C, exposed to 45°C for 30 min, and then returned to the 23°C chamber for recovery. The expression of Ccl5 in the skeletal muscle significantly decreased after 3 h of recovery. Serum CCL5 levels increased by approximately 1.9-fold after 30 min of heat exposure and then significantly decreased by approximately 0.7-fold after 23 h of recovery. This study suggests that heat stimulation decreases CCL5 secretion from the skeletal muscle in vitro and in vivo. Given its fundamental role in inflammation by recruiting several immune cells, CCL5 has a potential role in controlling inflammatory responses in the body after heat stimulation.
骨骼肌是一种内分泌器官，可产生蛋白质和肽，统称为肌因子。骨骼肌的温度在运动过程中或随环境温度变化而变化。然而，热刺激是否调节肌因子的分泌尚不清楚。因此，我们旨在探讨环境热刺激对肌因子分泌的影响。我们最初研究了 C2C12 肌管的分泌组，鉴定出了几种新的热响应肌因子。热应激使 C-C 基序趋化因子配体 5（CCL5）的浓度降低了 0.3 倍。在 C2C12 细胞 3 小时的热刺激后，热休克蛋白 70 的表达被诱导，并且 CCL5 的基因表达和分泌在 C2C12 细胞中显著减弱。然后，我们检查了急性热应激对小鼠血清 CCL5 水平和骨骼肌 Ccl5 基因表达的影响。将小鼠维持在 23°C，暴露于 45°C 30 分钟，然后返回 23°C 室进行恢复。恢复 3 小时后，骨骼肌中 Ccl5 的表达显著降低。热暴露 30 分钟后，血清 CCL5 水平增加约 1.9 倍，然后在 23 小时恢复后显著降低约 0.7 倍。这项研究表明，热刺激会减少体外和体内骨骼肌中 CCL5 的分泌。鉴于 CCL5 通过募集几种免疫细胞在炎症中起基本作用，它在热刺激后可能在控制体内炎症反应中发挥作用。
