Topically applied manganese-porphyrins BMX-001 and BMX-010 display a significant anti-inflammatory response in a mouse model of allergic dermatitis.
Topically applied manganese-porphyrins BMX-001 and BMX-010 display a significant anti-inflammatory response in a mouse model of allergic dermatitis.
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局部应用锰卟啉 BMX-001 和 BMX-010 在过敏性皮炎小鼠模型中显示出显着的抗炎反应。
DOI：
10.1007/s00403-016-1693-0
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发表时间：
2016
影响因子：
3
通讯作者：
Bäumer,Wolfgang
中科院分区：
文献类型：
--
作者：
Stover,Kelsey;Fukuyama,Tomoki;Young,AshlynT;Daniele,MichaelA;Oberley,Rebecca;Crapo,JamesD;Bäumer,Wolfgang
在这项研究中，我们局部给予两种抗氧化剂化合物，锰卟啉衍生物BMX-001和BMX-010，在小鼠变应性皮炎模型中，并比较了减少瘙痒和炎症的功效。初步分析了BMX-001和BMX-010对角质形成细胞、骨髓源性树突状细胞（bmdc）和t细胞的体外作用。为了评估搔抓行为，在化合物48/80或甲苯-2,4，-二异氰酸酯（TDI）刺激小鼠皮炎模型前16小时和/或1小时局部应用BMX-001和BMX-010（0.01和0.1%）。此外，在TDI模型中以类似的方式评估过敏性皮肤炎症。在TDI刺激24 h后测量处理后的穗厚，并与基础值进行比较。处死小鼠，取耳廓作进一步分析。在体外实验中，两种BMX物质均能显著抑制角质形成细胞的细胞因子产生以及BMDC和t细胞的增殖。在复方48/80模型中，局部用BMX乳膏治疗导致搔抓行为显著减少，但在TDI模型中没有。用BMX-001和BMX-010治疗的小鼠显示出中等剂量依赖性的耳厚减少，有趣的是，在所有治疗方案中，炎症皮肤中细胞因子IL-1β和IL-4的浓度降低了80 - 90%。这些初步结果表明BMX-001和BMX-010乳膏治疗过敏性炎症性皮肤病的潜在益处。
In this study, we topically administered two antioxidant compounds, the manganese-porphyrin-derivatives BMX-001 and BMX-010, in a mouse model of allergic dermatitis and compared the efficacy for reduction of itch and inflammation. In vitro effects of BMX-001 and BMX-010 on keratinocytes, bone marrow derived dendritic cells (BMDCs) and T-cells were initially analysed. For assessment of scratching behaviour, BMX-001 and BMX-010 (0.01 and 0.1 %) were topically applied 16 h and/or 1 h before compound 48/80 or toluene-2,4,-diisocyanate (TDI) challenge in a TDI induced mouse dermatitis model. Additionally, assessment of allergic skin inflammation was performed in a similar manner in the TDI model. Post-treatment ear thickness was measured 24 h after TDI challenge and compared to basal values. The mice were sacrificed and the ear auricle was removed for further analysis. In vitro, both BMX substances significantly inhibited cytokine production of keratinocytes as well as of BMDC and T-cell proliferation. Topical treatment with BMX cream resulted in a significant decrease in scratching behaviour in the compound 48/80 model, but not in the TDI model. Mice treated with BMX-001 and BMX-010 showed a moderate dose dependent decrease in ear thickness, and interestingly, the concentration of the cytokines IL-1β and IL-4 in inflamed skin was reduced by 80–90 % by all treatment options. These first results suggest the potential benefit of a BMX-001 and BMX-010 cream for the treatment of allergic-inflammatory skin diseases.