Andrographolide suppresses thymic stromal lymphopoietin in phorbol myristate acetate/calcium ionophore A23187-activated mast cells and 2,4-dinitrofluorobenzene-induced atopic dermatitis-like mice model.
Andrographolide suppresses thymic stromal lymphopoietin in phorbol myristate acetate/calcium ionophore A23187-activated mast cells and 2,4-dinitrofluorobenzene-induced atopic dermatitis-like mice model.
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DOI：
10.2147/dddt.s94056
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Yu H
中科院分区：
文献类型：
--
作者：
Li CX;Li HG;Zhang H;Cheng RH;Li M;Liang JY;Gu Y;Ling B;Yao ZR;Yu H
特应性皮炎（AD）是最常见的炎症性皮肤病之一。胸腺基质淋巴生成素（TSLP）已被证明是AD发病过程中一个重要的免疫因子。高水平的细胞内钙浓度和受体相互作用蛋白2/caspase-1/NF-κB通路的激活可诱导TSLP的产生。Andrographolide （Andrographolide， ANDRO）是一种天然双环二萜内酯，通过抑制NF-κB通路在胃肠道炎症性疾病中发挥抗炎作用。探讨ANDRO对人肥大细胞和AD小鼠模型中TSLP生成的影响。我们采用酶联免疫吸附法、实时逆转录聚合酶链反应法、Western blot法和免疫荧光染色法研究了ANDRO对AD的影响。ANDRO通过阻断人肥大细胞系1细胞中受体相互作用蛋白2/caspase-1/NF-κB通路，改善肉豆酸酯/钙离子载体A23187诱导的TSLP细胞内钙、蛋白和信使RNA水平的升高。通过口服或局部给药，安德罗还能减轻2,4-二硝基氟苯诱导的AD小鼠模型的临床症状，并抑制病变皮肤中TSLP的水平。综上所述，ANDRO可能通过抑制TSLP的表达而成为一种潜在的AD治疗剂。
Atopic dermatitis (AD) is one of the most common inflammatory cutaneous diseases. Thymic stromal lymphopoietin (TSLP) has been demonstrated to be an important immunologic factor in the pathogenesis of AD. The production of TSLP can be induced by a high level of intracellular calcium concentration and activation of the receptor-interacting protein 2/caspase-1/NF-κB pathway. Andrographolide (ANDRO), a natural bicyclic diterpenoid lactone, has been found to exert anti-inflammatory effects in gastrointestinal inflammatory disorders through suppressing the NF-κB pathway. To explore the effect of ANDRO on the production of TSLP in human mast cells and AD mice model. We utilized enzyme-linked immunosorbent assay, real-time reverse transcription polymerase chain reaction analysis, Western blot analysis, and immunofluorescence staining assay to investigate the effects of ANDRO on AD. ANDRO ameliorated the increase in the intracellular calcium, protein, and messenger RNA levels of TSLP induced by phorbol myristate acetate/calcium ionophore A23187, through the blocking of the receptor-interacting protein 2/caspase-1/NF-κB pathway in human mast cell line 1 cells. ANDRO, via oral or local administration, also attenuated clinical symptoms in 2,4-dinitrofluorobenzene-induced AD mice model and suppressed the levels of TSLP in lesional skin. Taken together, ANDRO may be a potential therapeutic agent for AD through suppressing the expression of TSLP.