BACKGROUND Dry skin itch is one of the most common skin diseases and elderly people are believed to be particularly prone to it. The inflammasome has been suggested to play an important role in chronic inflammatory disorders including inflammatory skin diseases such as psoriasis. However, little is known about the role of NLRP1 inflammasome in dry skin-induced chronic itch. METHODS Dry skin-induced chronic itch model was established by acetone-ether-water (AEW) treatment. Spontaneous scratching behavior was recorded by video monitoring. The expression of nucleotide oligomerization domain (NOD)-like receptor protein 1 (NLRP1) inflammasome complexes, transient receptor potential vanilloid type 1 (TRPV1), and the level of inflammatory cytokines were determined by western blot, quantitative real-time PCR, and enzyme-linked immunosorbent assay (ELISA) kits. Nlrp1a knockdown was performed by an adeno-associated virus (AAV) vector containing Nlrp1a-shRNA-eGFP infusion. H.E. staining was used to evaluate skin lesion. RESULTS AEW treatment triggers spontaneous scratching and significantly increases the expression of NLRP1, ASC, and caspase-1 and the levels of IL-1β, IL-18, IL-6, and TNF-α in the spinal cord and the skin of mice. Spinal cord Nlrp1a knockdown prevents AEW-induced NLRP1 inflammasome assembly, TRPV1 channel activation, and spontaneous scratching behavior. Capsazepine, a specific antagonist of TRPV1, can also inhibit AEW-induced inflammatory response and scratching behavior. Furthermore, elderly mice and female mice exhibited more significant AEW-induced scratching behavior than young mice and male mice, respectively. Interestingly, AEW-induced increases in the expression of NLRP1 inflammasome complex and the levels of inflammatory cytokines were more remarkable in elderly mice and female mice than in young mice and male mice, respectively. CONCLUSIONS Spinal cord NLRP1 inflammasome-mediated inflammatory response contributes to dry skin-induced chronic itch by TRPV1 channel, and it is also involved in age and sex differences of chronic itch. Inhibition of NLRP1 inflammasome may offer a new therapy for dry skin itch.

中文翻译：

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脊髓NLRP1炎性小体有助于小鼠皮肤干燥引起的慢性瘙痒。

背景技术皮肤瘙痒是最常见的皮肤疾病之一，并且据认为老年人特别容易发痒。已经表明，炎性小体在慢性炎性疾病包括牛皮癣等炎性皮肤疾病中起重要作用。但是，关于NLRP1炎性小体在皮肤干燥引起的慢性瘙痒中的作用了解甚少。方法采用丙酮醚水（AEW）处理建立干性皮肤慢性瘙痒模型。通过视频监控记录自发的刮擦行为。通过Western印迹，实时荧光定量PCR检测核苷酸寡聚化域（NOD）样受体蛋白1（NLRP1）炎性小体复合物的表达，瞬时受体电位香草样1型（TRPV1）和炎症细胞因子的水平，和酶联免疫吸附测定（ELISA）试剂盒。Nlrp1a敲低是通过包含Nlrp1a-shRNA-eGFP输注的腺伴随病毒（AAV）载体进行的。HE染色用于评估皮肤病变。结果AEW治疗会触发自发性抓挠，并显着增加小鼠脊髓和皮肤中NLRP1，ASC和caspase-1的表达以及IL-1β，IL-18，IL-6和TNF-α的水平。脊髓Nlrp1a敲低可防止AEW诱导的NLRP1炎症小体装配，TRPV1通道激活以及自发的抓挠行为。辣椒素，TRPV1的特异性拮抗剂，也可以抑制AEW诱导的炎症反应和抓挠行为。此外，老年小鼠和雌性小鼠分别表现出比年轻小鼠和雄性小鼠更显着的AEW诱导的抓挠行为。有趣的是 AEW引起的老年小鼠和雌性小鼠的NLRP1炎性小体复合物表达和炎性细胞因子水平的增加分别比年轻小鼠和雄性小鼠显着。结论脊髓NLRP1炎性体介导的炎症反应通过TRPV1通道促进皮肤干燥引起的慢性瘙痒，并且还参与了慢性瘙痒的年龄和性别差异。抑制NLRP1炎性体可能为干性皮肤瘙痒提供一种新疗法。并且它也与慢性瘙痒的年龄和性别差异有关。抑制NLRP1炎性体可能为干性皮肤瘙痒症提供一种新疗法。并且它也与慢性瘙痒的年龄和性别差异有关。抑制NLRP1炎性体可能为干性皮肤瘙痒症提供一种新疗法。