Key Laboratory of Biorheological Science and Technology, College of Bioengineering, Ministry of Education, Chongqing University, Chongqing, 400044, China.
School of Life Science, Chongqing University, Chongqing, 400044, People's Republic of China.
Inflammation. 2018 Oct;41(5):1731-1743. doi: 10.1007/s10753-018-0816-5.
Modern molecular techniques have highlighted the presence of inflammation throughout the spectrum of tendinopathy. Previous studies have suggested that excessive inflammation in the tendon is a major factor leading to poor clinical treatment. Furthermore, the NLRP3 inflammasome, as a new term, is closely associated with the pathogenesis of many diseases. In the present study, we examined whether the NLRP3 inflammasome contributes to the development of tendinitis and whether cyclic stretching plays a prominent role in inflammation in the tendon. In the present study, we showed that hydrogen peroxide (HO) remarkably enhances the expression and release of IL-1β, TNF-α, and IL-6. The maturation of IL-1β, induced by HO, depends on the activation of the NLRP3 inflammasome. Cyclic stretching enhances the maturation of IL-1β via promoting HO-induced NLRP3 inflammasome activation in tenocytes. Furthermore, we also found that the depolymerization of filamentous actin (F-actin) was required for cyclic stretching-enhanced NLRP3 inflammasome activation. The present study suggests that NLRP3 inflammasome plays an important regulatory role in the pathogenesis of tendinitis. Disruption of the cytoskeleton by cyclic stretching exerts a proinflammatory effect via further activating the NLRP3/IL-1β pathway and hence contributes to tendinitis. These results may provide theoretical support for a new treatment strategy for preventing excessive inflammation in the tendon.
现代分子技术已经强调了炎症在整个肌腱病谱中的存在。以前的研究表明，肌腱内过度的炎症是导致临床治疗效果不佳的一个主要因素。此外，NLRP3 炎性小体作为一个新术语，与许多疾病的发病机制密切相关。在本研究中，我们研究了 NLRP3 炎性小体是否参与了腱炎的发展，以及周期性拉伸是否在肌腱炎症中起重要作用。在本研究中，我们发现过氧化氢（HO）显著增强了 IL-1β、TNF-α 和 IL-6 的表达和释放。HO 诱导的 IL-1β 的成熟依赖于 NLRP3 炎性小体的激活。周期性拉伸通过促进 HO 诱导的 tenocytes 中 NLRP3 炎性小体的激活来增强 IL-1β 的成熟。此外，我们还发现丝状肌动蛋白（F-actin）的解聚对于周期性拉伸增强的 NLRP3 炎性小体激活是必需的。本研究表明，NLRP3 炎性小体在肌腱病的发病机制中起着重要的调节作用。周期性拉伸破坏细胞骨架通过进一步激活 NLRP3/IL-1β 通路发挥促炎作用，从而导致腱炎。这些结果可能为预防肌腱过度炎症的新治疗策略提供理论支持。
