目的:熊去氧胆酸(UDCA)是一种用于胆汁淤积性肝病的亲水性二羟基胆汁酸,具有抗氧化剂,抗肿瘤,和抗炎作用。然而,其对特应性皮炎(AD)的潜在影响尚未阐明。本研究旨在评估UDCA在抑制AD样小鼠炎症反应和减轻病变中的功效。
方法:为了研究UDCA在AD样炎症反应中的疗效,采用肿瘤坏死因子-α(TNF-α)和干扰素-γ(IFN-γ)刺激的HaCaT细胞和抗二硝基苯免疫球蛋白E(DNP-IgE)和人血清白蛋白(HSA)刺激的RBL-2H3细胞来研究炎症因子的水平及其机制。通过将DNCB/DFE应用于小鼠诱导AD样病变。通过评估器官重量来分析UDCA在AD样小鼠中的作用,血清IgE和炎性细胞因子水平,和组织病理学改变使用免疫组织化学和免疫荧光染色。
结果:在HaCaT细胞中,UDCA显著降低TARC,MDC,MCP-1和IL-6的表达通过抑制核NF-κB和细胞质IκB的磷酸化,也增加了皮肤屏障蛋白的水平。在RBL-2H3细胞中,UDCA降低β-己糖胺酶和IL-4水平。在类似AD的老鼠中,UDCA抑制器官肥大,耳朵水肿,SCORAD指数,DFE特异性IgE水平,炎性细胞因子水平,皮肤肥大,肥大细胞入侵,皮肤屏障丧失,和胸腺基质淋巴细胞生成素阳性区域。
结论:UDCA抑制角质形成细胞和肥大细胞中促炎细胞因子的表达。它还通过抑制AD样小鼠的症状而没有器官毒性来减轻特应性。UDCA可能是AD的有效和安全的治疗方法。
OBJECTIVE: Ursodeoxycholic acid (UDCA) is a hydrophilic dihydroxy bile acid used for cholestatic liver disease and exhibits antioxidant, antitumor, and anti-inflammatory effects. However, its potential effects on atopic dermatitis (AD) have not been elucidated. This study aimed to evaluate the efficacy of UDCA in inhibiting the inflammatory response and alleviating lesions in AD-like mice.
METHODS: To investigate the efficacy of UDCA in AD-like inflammatory responses, tumor necrosis factor-alpha (TNF-α)- and interferon-gamma (IFN-γ)-stimulated HaCaT cells and anti-dinitrophenyl immunoglobulin E (DNP-IgE)- and human serum albumin (HSA)-stimulated RBL-2H3 cells were used to investigate the levels of inflammatory factors and their mechanisms. AD-like lesions were induced by applying DNCB/DFE to mice. The effect of UDCA administration in AD-like mice was analyzed by assessing organ weight, serum IgE and inflammatory cytokine levels, and histopathological changes using immunohistochemical and immunofluorescent staining.
RESULTS: In HaCaT cells, UDCA significantly diminished TARC, MDC, MCP-1, and IL-6 expression by inhibiting the phosphorylation of nuclear NF-κB and cytoplasmic IκB, and also increased the levels of skin barrier protein. In RBL-2H3 cells, UDCA reduced β-hexosaminidase and IL-4 levels. In AD-like mice, UDCA suppressed organ hypertrophy, ear edema, SCORAD index, DFE-specific IgE levels, inflammatory cytokine levels, skin hypertrophy, mast cell invasion, skin barrier loss, and thymic stromal lymphopoietin-positive areas.
CONCLUSIONS: UDCA suppressed the expression of pro-inflammatory cytokines by keratinocytes and mast cells. It also alleviated atopy by suppressing symptoms without organ toxicity in AD-like mice. UDCA may be an effective and safe treatment for AD.