Lim Doo-Ho, Lee Eun-Ju, Lee Hee-Seop, Kim Do Hoon, Lee Jae-Hyun, Jeong Mi Ryeong, Hong Seokchan, Lee Chang-Keun, Yoo Bin, Youn Jeehee, Kim Yong-Gil
Division of Rheumatology, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, Korea.
Asan Institute for Life Science, Asan Medical Center, Seoul 05505, Korea.
Biomedicines. 2021 Aug 27;9(9):1095. doi: 10.3390/biomedicines9091095.
Acetylated diacylglycerol 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) is a lipid molecule from the antlers of sika deer that might reduce inflammation by effectively controlling neutrophil infiltration, endothelial permeability and inflammatory chemokine production. Therefore, we evaluated the modulatory effect of PLAG on arthritis and interstitial lung disease (ILD) in an autoimmune arthritis model. We injected curdlan into SKG mice and PLAG was orally administered every day from 3 weeks to 20 weeks after the curdlan injection. The arthritis score was measured every week after the curdlan injection. At 20 weeks post-injection, the lung specimens were evaluated with H&E, Masson's trichrome and multiplexed immunofluorescent staining. Serum cytokines were also analyzed using a Luminex multiple cytokine assay. PLAG administration decreased the arthritis score until 8 weeks after the curdlan injection. However, the effect was not sustained thereafter. A lung histology revealed severe inflammation and fibrosis in the curdlan-induced SKG mice, which was attenuated in the PLAG-treated mice. Furthermore, immunofluorescent staining of the lung tissue showed a GM-CSF neutrophil accumulation and a decreased citrullinated histone 3 expression after PLAG treatment. PLAG also downregulated the levels of IL-6 and TNF-α and upregulated the level of sIL-7Rα, an anti-fibrotic molecule. Our results indicate that PLAG might have a preventative effect on ILD development through the resolution of NETosis in the lung.
乙酰化二酰甘油1-棕榈酰-2-亚油酰-3-乙酰-rac-甘油（PLAG）是一种来自梅花鹿角的脂质分子，它可能通过有效控制中性粒细胞浸润、内皮通透性和炎症趋化因子产生来减轻炎症。因此，我们在自身免疫性关节炎模型中评估了PLAG对关节炎和间质性肺病（ILD）的调节作用。我们向SKG小鼠注射了可德胶，并在注射可德胶后第3周开始至第20周每天口服PLAG。在注射可德胶后每周测量关节炎评分。在注射后20周，用苏木精-伊红染色、马松三色染色和多重免疫荧光染色对肺组织标本进行评估。还使用Luminex多细胞因子检测法分析血清细胞因子。在注射可德胶后8周内，PLAG给药降低了关节炎评分。然而，此后该效果未持续。肺组织学检查显示，可德胶诱导的SKG小鼠出现严重炎症和纤维化，而PLAG治疗的小鼠中这种情况有所减轻。此外，肺组织的免疫荧光染色显示，PLAG治疗后GM-CSF中性粒细胞积聚减少，瓜氨酸化组蛋白3表达降低。PLAG还下调了IL-6和TNF-α的水平，并上调了抗纤维化分子sIL-7Rα的水平。我们的结果表明，PLAG可能通过解决肺中的中性粒细胞胞外陷阱形成对ILD的发展具有预防作用。
