Extended characterization of IL-33/ST2 as a predictor for wound age determination in skin wound tissue samples of humans and mice
Extended characterization of IL-33/ST2 as a predictor for wound age determination in skin wound tissue samples of humans and mice
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DOI：
10.1007/s00414-023-03025-x
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发表时间：
2023-05-29
影响因子：
2.1
通讯作者：
Tao，Luyang
中科院分区：
文献类型：
--
作者：
Gao，Yuan;Cai，Luwei;Tao，Luyang
白细胞介素（IL）-33（IL-33）是一种重要的炎症细胞因子，在人和小鼠的皮肤创伤组织和血清中高度表达，在皮肤创伤愈合（SWH）过程中起重要作用，依赖于IL-33/抑瘤2（ST2）通路。然而，IL-33和ST 2本身以及它们的相互作用是否可以应用于法医实践中的皮肤伤口年龄确定仍然不完全。收集了几分钟至24小时（hs）的损伤间隔的人皮肤样品和1小时至14天（ds）的损伤间隔的小鼠皮肤样品。在此，结果表明IL-33和ST 2在人皮肤伤口中增加，并且在小鼠皮肤伤口中，随时间增加，IL-33表达在24 hs和10 ds达到峰值，ST 2表达在12 hs和7 ds达到峰值。值得注意的是，IL-33和ST 2蛋白的相对量<0.35表明伤口年龄为3小时;它们的相对量> 1.0表明小鼠皮肤伤口后伤口年龄为24小时。此外，免疫荧光染色结果显示，IL-33和ST 2在有或无皮肤创伤的F4/80阳性巨噬细胞和CD 31阳性血管内皮细胞的胞浆中一致表达，而在有皮肤创伤的α-SMA阳性肌成纤维细胞中IL-33的核定位缺失。有趣的是，IL-33给药通过增加细胞角蛋白（K）14阳性角化细胞和波形蛋白阳性成纤维细胞的增殖促进伤口区域闭合。相反，用其拮抗剂（即，抗IL-33）或受体拮抗剂（例如，anti-ST2）加重了上述病理变化。此外，用IL-33与抗IL-33或抗ST 2组合的治疗逆转了IL-33促进皮肤伤口闭合的作用，表明IL-33施用通过IL-33/ST 2信号传导途径促进皮肤伤口闭合。总的来说，这些研究结果表明，IL-33/ST 2的检测可能是一个可靠的生物标志物，用于确定皮肤伤口的法医实践中的年龄。
Interleukin (IL)-33, an important inflammatory cytokine, is highly expressed in skin wound tissue and serum of humans and mice, and plays an essential role in the process of skin wound healing (SWH) dependent on the IL-33/suppression of tumorigenicity 2 (ST2) pathway. However, whether IL-33 and ST2 themselves, as well as their interaction, can be applied for skin wound age determination in forensic practice remains incompletely characterized. Human skin samples with injured intervals of a few minutes to 24 hours (hs) and mouse skin samples with injured intervals of 1 h to 14 days (ds) were collected. Herein, the results demonstrated that IL-33 and ST2 are increased in the human skin wounds, and that in mice skin wounds, there is an increase over time, with IL-33 expression peaking at 24 hs and 10 ds, and ST2 expression peaking at 12 hs and 7 ds. Notably, the relative quantity of IL-33 and ST2 proteins < 0.35 suggested a wound age of 3 hs; their relative quantity > 1.0 suggested a wound age of 24 hs post-mouse skin wounds. In addition, immunofluorescent staining results showed that IL-33 and ST2 were consistently expressed in the cytoplasm of F4/80-positive macrophages and CD31-positive vascular endothelial cells with or without skin wounds, whereas nuclear localization of IL-33 was absent in α-SMA-positive myofibroblasts with skin wounds. Interestingly, IL-33 administration facilitated the wound area closure by increasing the proliferation of cytokeratin (K) 14 -positive keratinocytes and vimentin-positive fibroblasts. In contrast, treating with its antagonist (i.e., anti-IL-33) or receptor antagonist (e.g., anti-ST2) exacerbated the aforementioned pathological changes. Moreover, treatment with IL-33 combined with anti-IL-33 or anti-ST2 reversed the effect of IL-33 on facilitating skin wound closure, suggesting that IL-33 administration facilitated skin wound closure through the IL-33/ST2 signaling pathway. Collectively, these findings indicate that the detection of IL-33/ST2 might be a reliable biomarker for the determination of skin wound age in forensic practice.