Anti-inflammatory effects of amarogentin on 2,4-dinitrochlorobenzene-induced atopic dermatitis-like mice and in HaCat cells.
Anti-inflammatory effects of amarogentin on 2,4-dinitrochlorobenzene-induced atopic dermatitis-like mice and in HaCat cells.
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DOI：
10.1002/ame2.12260
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发表时间：
2023-06
影响因子：
3.7
通讯作者：
Chen, Si
中科院分区：
文献类型：
--
作者：
Zhang, Qian;Wang, Hanlin;Ran, Cheng;Lyu, Yansi;Li, Fei;Yao, Yihang;Xing, Shaojun;Wang, Li;Chen, Si
Amarogentin（AMA）是从獐牙菜属和龙胆属植物根中提取的开环环烯醚萜苷，具有抗氧化、抗炎、抗肿瘤等多种生物活性。特应性皮炎（AD）是一种由多种炎性细胞因子调节紊乱引起的慢性炎症性皮肤病。目前尚未发现有效的治疗AD的方法。我们构建了HaCat和脾细胞模型，并使用酶联免疫吸附试验（ELISA）检测了AMA对IL-4，IL-6和IL-13分泌的抑制作用。建立AD小鼠模型，给予AMA治疗，观察皮损严重程度，取表皮组织，苏木精-伊红染色观察表皮厚度，甲苯胺蓝染色观察肥大细胞浸润情况。采用免疫组化和Western blot分析检测激肽释放酶相关肽酶7（KLK 7）和聚丝蛋白（FLG）的表达。采用定量聚合酶链反应（qPCR）检测KLK 7和FLG的mRNA表达。检测血免疫球蛋白E（IgE）分泌。AMA抑制肿瘤坏死因子（TNF）-α诱导的HaCaT细胞分泌的IL-6，并减少植物血凝素（PHA）诱导的小鼠脾脏原代细胞分泌的IL-4和IL-13。发现AMA治疗2，4-二硝基氯苯诱导的AD样小鼠可促进皮炎的恢复，降低皮炎严重程度评分和抓挠次数，治疗皮损，减少表皮厚度，减少肥大细胞浸润，降低血清IgE水平，降低AD相关细胞因子的表达水平，增加FLG蛋白和mRNA的表达，并降低AD样小鼠皮肤组织中KLK 7的蛋白和mRNA表达。总之，AMA在细胞水平抑制炎症反应，AMA降低特异性皮炎小鼠的验证反应，缓解瘙痒，修复受损的皮肤屏障。本研究证实了AMA在体内和体外对特应性皮炎的治疗作用。我们证实AMA可以抑制HaCaT细胞和小鼠肾细胞IL-4、6和13的表达。在AD小鼠模型中，采用H&E、TB染色、免疫组化、Western blot、qPCR和ELISA等方法证实AMA对AD的影响。
Amarogentin (AMA) is a secoiridoid glycoside extracted from Swertia and Gentiana roots and exhibits many biological effects such as antioxidative, anti‐inflammatory, and antitumor activities. Atopic dermatitis (AD) is a chronic inflammatory skin disease caused by disorders in the regulation of multiple inflammatory cytokines. No effective cure has been found for AD now. We constructed the HaCat and splenocyte model and tested the inhibitory effect of AMA on IL‐4, IL‐6, and IL‐13 secretions using enzyme‐linked immunosorbent assay (ELISA). The AD mouse model was constructed and treated with AMA, the severity of skin lesions was observed, epidermal tissue was collected, and epidermal thickness and mast cell infiltration were observed using hematoxylin and eosin and toluidine blue staining, respectively. The expression of kallikrein‐related peptidase 7 (KLK7) and filaggrin (FLG) was detected using immunostaining and Western blot analysis. The mRNA expression of KLK7 and FLG was detected using quantitative polymerase chain reaction (qPCR). Blood immunoglobulin E (IgE) secretion was detected. AMA inhibited IL‐6 secreted by tumor necrosis factor (TNF)‐α‐induced HaCaT cells and reduced IL‐4 and IL‐13 secreted by phytohemagglutinin (PHA)‐induced primary cells in the mice spleen. It was found that the treatment of AMA with 2,4‐dinitrochlorobenzene‐induced AD‐like mice could promote the recovery of dermatitis, reduce the score of dermatitis severity and the scratching frequency, treat the skin lesions, reduce the epidermal thickness, decrease the infiltration of mast cells, reduce the IgE level in serum, decrease the expression levels of AD‐related cytokines, increase protein and mRNA expression of FLG, and reduce the protein and mRNA expression of KLK7 in the skin tissues of AD‐like mice. In conclusion, AMA inhibits inflammatory response at the cellular level, and AMA reduces the validation response of specific dermatitis mice, relieves pruritus, and repairs the damaged skin barrier. This study confirmed the therapeutic effect of AMA on atopic dermatitis in vivo and in vitro. We confirmed that AMA can inhibit the expression of IL‐4, 6 and 13 with HaCaT cells and mouse kidney cells. In AD mouse model, H&E, TB staining, immunohistochemistry, Western blot, qPCR and ELISA were used to confirm the effect of AMA on AD.
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DOI：
10.1084/jem.20082242
发表时间：
2009-05-11
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Briot A;Deraison C;Lacroix M;Bonnart C;Robin A;Besson C;Dubus P;Hovnanian A
通讯作者：
Hovnanian A
DOI：
10.4168/aair.2018.10.3.207
发表时间：
2018-05
期刊：
Allergy, asthma & immunology research
影响因子：
--
作者：
Kim BE;Leung DYM
通讯作者：
Leung DYM
影响因子：
--
作者：
Ku JM;Hong SH;Kim HI;Seo HS;Shin YC;Ko SG
通讯作者：
Ko SG
影响因子：
14.2
作者：
Hanifin, JM;Tofte, SJ
通讯作者：
Tofte, SJ
影响因子：
3.4
作者：
Huang, Xia;Xu, Bo
通讯作者：
Xu, Bo