Chiu Hui-Wen, Chen Cheng-Hsien, Chang Jen-Ning, Chen Chien-Hsiung, Hsu Yung-Ho
Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, No. 291, Zhongzeng Rd., Zhonghe District, New Taipei City, 23561, Taiwan.
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
J Mol Med (Berl). 2016 Jul;94(7):809-19. doi: 10.1007/s00109-016-1389-0. Epub 2016 Feb 11.
Understanding the underlying molecular mechanisms in burn wound progression is crucial to providing appropriate diagnoses and designing therapeutic regimens for burn patients. When inflammation becomes unregulated, recurrent, or excessive, it interferes with burn wound healing. Autophagy, which is a homeostatic and catabolic degradation process, was found to protect against ischemic injury, inflammatory diseases, and apoptosis in some cases. In the present study, we investigated whether far-infrared (FIR) could ameliorate burn wound progression and promote wound healing both in vitro and in a rat model of deep second-degree burn. We found that FIR induced autophagy in differentiated THP-1 cells (human monocytic cells differentiated to macrophages). Furthermore, FIR inhibited both the NLRP3 inflammasome and the production of IL-1β in lipopolysaccharide-activated THP-1 macrophages. In addition, FIR induced the ubiquitination of ASC, which is the adaptor protein of the inflammasome, by increasing tumor necrosis factor receptor-associated factor 6 (TRAF6), which is a ubiquitin E3 ligase. Furthermore, the exposure to FIR then promoted the delivery of inflammasome to autophagosomes for degradation. In a rat burn model, FIR ameliorated burn-induced epidermal thickening, inflammatory cell infiltration, and loss of distinct collagen fibers. Moreover, FIR enhanced autophagy and suppressed the activity of the NLRP3 inflammasome in the rat skin tissue of the burn model. Based on these results, we suggest that FIR-regulated autophagy and inflammasomes will be important for the discovery of novel therapeutics to promote the healing of burn wounds.
Far-infrared (FIR) induced autophagy in THP-1 macrophages. FIR suppressed the NLRP3 inflammasome through the activation of autophagy. FIR induced the ubiquitination of ASC by increasing TRAF6. FIR ameliorated burn wound progression and promoted wound healing in a rat burn model.
了解烧伤创面进展的潜在分子机制对于为烧伤患者提供适当诊断和设计治疗方案至关重要。当炎症变得失控、反复或过度时，会干扰烧伤创面愈合。自噬是一种稳态和分解代谢的降解过程，在某些情况下被发现可预防缺血性损伤、炎症性疾病和细胞凋亡。在本研究中，我们调查了远红外线（FIR）是否能在体外和深二度烧伤大鼠模型中改善烧伤创面进展并促进伤口愈合。我们发现FIR在分化的THP-1细胞（分化为巨噬细胞的人单核细胞）中诱导自噬。此外，FIR抑制脂多糖激活的THP-1巨噬细胞中的NLRP3炎性小体和IL-1β的产生。此外，FIR通过增加作为泛素E3连接酶的肿瘤坏死因子受体相关因子6（TRAF6）诱导炎性小体衔接蛋白ASC的泛素化。此外，暴露于FIR随后促进炎性小体向自噬体的递送以进行降解。在大鼠烧伤模型中，FIR改善了烧伤引起的表皮增厚、炎性细胞浸润和明显胶原纤维的丧失。此外，FIR增强了自噬并抑制了烧伤模型大鼠皮肤组织中NLRP3炎性小体的活性。基于这些结果，我们认为FIR调节的自噬和炎性小体对于发现促进烧伤创面愈合的新型疗法将很重要。
远红外线（FIR）在THP-1巨噬细胞中诱导自噬。FIR通过激活自噬抑制NLRP3炎性小体。FIR通过增加TRAF6诱导ASC的泛素化。FIR改善了大鼠烧伤模型中的烧伤创面进展并促进伤口愈合。
