Hirunsai Muthita, Srikuea Ratchakrit
Department of Biopharmacy, Faculty of Pharmacy, Srinakharinwirot University, Nakhon Nayok, Thailand.
Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
J Appl Physiol (1985). 2020 Mar 1;128(3):612-626. doi: 10.1152/japplphysiol.00594.2019. Epub 2020 Feb 13.
During disuse-induced muscle atrophy, macrophages play a significant role in inflammatory responses that occur with muscle degeneration and repair. Heat treatment has been shown to alleviate muscle atrophy; however, the effect of heat on inflammatory responses following tenotomy has not been evaluated. This study examined the effects of heat stress on proinflammatory (M1-like) and anti-inflammatory (M2-like) macrophage populations. Also, cytokine protein expression in oxidative soleus and glycolytic plantaris muscles following Achilles tendon transection (tenotomy) was analyzed. Male Wistar rats were assigned into control, control plus heat stress, tenotomy, and tenotomy plus heat stress groups. Tenotomy was performed for 8 (TEN8) and 14 (TEN14) days to induce muscle inflammation. Heat treatments, 30 min at 40.5-41.5°C, were given 24 h before and 1-6 consecutive days after tenotomy (TEN8 group) or every other day (TEN14 group). Tenotomy induced muscle necrosis, extensive infiltration of M1- (CD68), and M2- (CD163) like macrophages and increased tumor necrosis factor-α (TNFα) but not interleukin-10 (IL-10) protein expression. Heat stress caused a reduction in necrotic fibers, M1-like macrophage invasion, and TNFα protein expression in tenotomized soleus muscle. Additionally, heat stress enhanced M2-like macrophage accumulation during the 14 days following tenotomy in soleus muscle but did not affect IL-10 protein level. Our results indicate that heat stress can limit tenotomy-induced inflammatory responses through modulation of macrophage subtypes and TNFα protein expression, preferentially in oxidative muscle. These findings shed light on the ability of heat stress as a therapeutic strategy to manipulate macrophages for optimal inflammation during muscle atrophy. We investigated differential effects of heat stress on modulating inflammation following 8 and 14 days of tenotomy in soleus and plantaris muscles. Heat exposure could reduce necrosis, suppress pro-inflammatory macrophage infiltration, and diminish TNFα protein expression in tenotomized muscle, which preferentially occurred in soleus muscle. Additionally, heat stress enhanced anti-inflammatory macrophages in soleus muscle in the 14-day study period. Neither tenotomy nor heat stress had an impact on IL-10 protein expression in either muscle examined.
在废用性肌肉萎缩过程中，巨噬细胞在肌肉退变和修复时发生的炎症反应中起重要作用。热处理已被证明可减轻肌肉萎缩；然而，热对跟腱切断术后炎症反应的影响尚未得到评估。本研究检测了热应激对促炎（M1样）和抗炎（M2样）巨噬细胞群体的影响。此外，还分析了跟腱横断（跟腱切断术）后比目鱼肌（氧化型）和跖肌（糖酵解型）中细胞因子蛋白的表达。将雄性Wistar大鼠分为对照组、对照组加 热应激组、跟腱切断术组和跟腱切断术加热应激组。进行跟腱切断术8天（TEN8）和14天（TEN14）以诱导肌肉炎症。在跟腱切断术前24小时以及跟腱切断术后连续1 - 6天（TEN8组）或隔天（TEN14组）进行30分钟、40.5 - 41.5°C的热处理。跟腱切断术诱导了肌肉坏死、M1（CD68）和M2（CD163）样巨噬细胞的广泛浸润，并增加了肿瘤坏死因子-α（TNFα）的表达，但白细胞介素-10（IL-10）蛋白表达未增加。热应激导致切断跟腱的比目鱼肌中坏死纤维减少、M1样巨噬细胞浸润减少以及TNFα蛋白表达降低。此外,热应激在跟腱切断术后14天内增强了比目鱼肌中M2样巨噬细胞的积聚，但不影响IL-10蛋白水平。我们的结果表明，热应激可通过调节巨噬细胞亚型和TNFα蛋白表达来限制跟腱切断术诱导的炎症反应，在氧化型肌肉中尤为明显。这些发现揭示了热应激作为一种治疗策略在肌肉萎缩期间调节巨噬细胞以实现最佳炎症反应的能力。我们研究了热应激对跟腱切断术8天和14天后比目鱼肌和跖肌炎症调节的不同影响。热暴露可减少坏死、抑制促炎巨噬细胞浸润，并降低切断跟腱肌肉中的TNFα蛋白表达，这在比目鱼肌中更为明显。此外，在为期14天的研究中，热应激增强了比目鱼肌中的抗炎巨噬细胞。跟腱切断术和热应激均未对所检测的任何一块肌肉中的IL-10蛋白表达产生影响。
