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首页> 外文期刊>Journal of Translational Medicine >Immune-mediated changes in actinic keratosis following topical treatment with imiquimod 5% cream
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Immune-mediated changes in actinic keratosis following topical treatment with imiquimod 5% cream

机译：咪喹莫特5％乳膏局部治疗后免疫介导的光化性角化病变化

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Background The objective of this study was to identify the molecular processes responsible for the anti-lesional activity of imiquimod in subjects with actinic keratosis using global gene expression profiling. Methods A double-blind, placebo-controlled, randomized study was conducted to evaluate gene expression changes in actinic keratosis treated with imiquimod 5% cream. Male subjects (N = 17) with ≥ 5 actinic keratosis on the scalp applied placebo cream or imiquimod 3 times a week on nonconsecutive days for 4 weeks. To elucidate the molecular processes involved in actinic keratosis lesion regression by imiquimod, gene expression analysis using oligonucleotide arrays and real time reverse transcriptase polymerase chain reaction were performed on shave biopsies of lesions taken before and after treatment. Results Imiquimod modulated the expression of a large number of genes important in both the innate and adaptive immune response, including increased expression of interferon-inducible genes with known antiviral, anti-proliferative and immune modulatory activity, as well as various Toll-like receptors. In addition, imiquimod increased the expression of genes associated with activation of macrophages, dendritic cells, cytotoxic T cells, and natural killer cells, as well as activation of apoptotic pathways. Conclusion Data suggest that topical application of imiquimod stimulates cells in the skin to secrete cytokines and chemokines that lead to inflammatory cell influx into the lesions and subsequent apoptotic and immune cell-mediated destruction of lesions.
机译：背景技术这项研究的目的是使用整体基因表达谱分析来确定咪喹莫特在光化性角化病患者中抗病变活性的分子过程。方法进行了一项双盲，安慰剂对照的随机研究，以评估用5％咪喹莫特乳膏治疗的光化性角化病的基因表达变化。男性受试者（N = 17）在头皮上有≥5个光化性角化病，每周连续3次，每周3次应用安慰剂乳膏或咪喹莫特，连续4周。为了阐明通过咪喹莫特进行的光化性角化病病变消退的分子过程，对治疗前后进行的剃刮活检进行了使用寡核苷酸阵列和实时逆转录酶聚合酶链反应的基因表达分析。结果咪喹莫特调节了大量对先天和适应性免疫应答均重要的基因的表达，包括具有已知抗病毒，抗增殖和免疫调节活性的干扰素诱导基因的表达增加，以及各种Toll样受体。此外，咪喹莫特增加了与巨噬细胞，树突状细胞，细胞毒性T细胞和自然杀伤细胞活化以及凋亡途径活化相关的基因表达。结论数据表明，局部应用咪喹莫特可刺激皮肤细胞分泌细胞因子和趋化因子，从而导致炎性细胞大量流入病灶，并随后引起凋亡和免疫细胞介导的病灶破坏。

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