Department of Dermatology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Int J Dermatol. 2012 Sep;51(9):1116-22. doi: 10.1111/j.1365-4632.2011.05382.x. Epub 2012 Feb 20.
Imiquimod, an immune-response modifier, has been proven to be clinically effective in the treatment of viral infections and skin cancers, but its mechanism of action remains poorly understood. This study aimed to assess the effects of imiquimod on the expression of three immunity-related cytokines, TNF-α, IL-1β, and IL-6.
Female BALB/C mice were treated for seven days with topical 1% imiquimod cream; they were then killed and skin samples were snap-frozen. In the in vitro studies, both purified LCs and HaCaT cells were incubated with 5 μg/ml imiquimod for four hours. In all samples, the mRNA levels of TNF-α, IL-1β, and IL-6 were then detected by reverse transcription polymerase chain reaction, and the secretion levels were determined by an enzyme-linked immunosorbent assay.
Imiquimod upregulated the mRNA and protein expression levels of TNF-α, IL-1β, and IL-6 in the skin of imiquimod-treated BALB/C mice and in human LCs, compared with untreated controls (P<0.05). However, there was no significant difference in the expression of these cytokines in imiquimod-treated and untreated HaCaT cells.
These findings indicate that imiquimod increased the expression of TNF-α, IL-1β, and IL-6 in skin and that the target cell of imiquimod may be the LCs but is unlikely to be the epidermal keratinocytes.
咪喹莫特是一种免疫反应调节剂,已被证明在治疗病毒感染和皮肤癌方面具有临床疗效,但作用机制仍不清楚。本研究旨在评估咪喹莫特对三种免疫相关细胞因子 TNF-α、IL-1β 和 IL-6 表达的影响。
雌性 BALB/C 小鼠接受为期七天的 1%咪喹莫特乳膏外用治疗;然后处死并采集皮肤样本进行冷冻。在体外研究中,均将纯化的 LC 和 HaCaT 细胞与 5μg/ml 咪喹莫特孵育四小时。在所有样本中,通过逆转录聚合酶链反应检测 TNF-α、IL-1β 和 IL-6 的 mRNA 水平,并通过酶联免疫吸附试验测定其分泌水平。
与未处理对照组相比,咪喹莫特处理的 BALB/C 小鼠皮肤和人 LC 中 TNF-α、IL-1β 和 IL-6 的 mRNA 和蛋白表达水平上调(P<0.05)。然而,咪喹莫特处理和未处理 HaCaT 细胞中这些细胞因子的表达没有显著差异。
这些发现表明咪喹莫特增加了皮肤中 TNF-α、IL-1β 和 IL-6 的表达,咪喹莫特的靶细胞可能是 LC,而不是表皮角质形成细胞。