Immune-mediated changes in actinic keratosis following topical treatment with imiquimod 5% cream.
Immune-mediated changes in actinic keratosis following topical treatment with imiquimod 5% cream.
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DOI：
10.1186/1479-5876-5-7
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发表时间：
2007-01-26
影响因子：
7.4
通讯作者：
Birmachu W
中科院分区：
文献类型：
--
作者：
Torres A;Storey L;Anders M;Miller RL;Bulbulian BJ;Jin J;Raghavan S;Lee J;Slade HB;Birmachu W
这项研究的目的是通过全球基因表达谱确定咪喹莫特在光化性角化病患者中的抗皮损活性的分子过程。一项双盲、安慰剂对照、随机研究被用来评估5%咪喹莫特乳膏治疗光化性角化病的基因表达变化。17例头皮≥5光化性角化病的男性受试者使用安慰剂乳膏或咪喹莫特，每周3次，连续4周。为阐明咪喹莫特消退光化性角化病皮损的分子过程，采用寡核苷酸芯片和实时逆转录聚合酶链式反应对治疗前后的皮损进行基因表达分析。咪喹莫特调节了大量先天和获得性免疫反应中重要基因的表达，包括具有抗病毒、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样受体的表达。此外，咪喹莫特还增加了巨噬细胞、树突状细胞、细胞毒性T细胞和自然杀伤细胞激活相关基因的表达，以及凋亡途径的激活。数据表明，局部应用咪喹莫特刺激皮肤细胞分泌细胞因子和趋化因子，导致炎症细胞涌入皮损，随后发生凋亡和免疫细胞介导的皮损破坏。
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. 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. 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. 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.
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影响因子：
--
作者：
Fu, W;Cockerell, CJ
通讯作者：
Cockerell, CJ
影响因子：
6.4
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通讯作者：
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