Advanced Characterization of Imiquimod-Induced Psoriasis-Like Mouse Model.

Advanced Characterization of Imiquimod-Induced Psoriasis-Like Mouse Model.
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DOI:
10.3390/pharmaceutics12090789
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发表时间:
2020-08-20
期刊:
影响因子:
5.4
通讯作者:
Lamrayah M
Lamrayah M
中科院分区:
医学2区
文献类型:
--
作者:
Jabeen M;Boisgard AS;Danoy A;El Kholti N;Salvi JP;Boulieu R;Fromy B;Verrier B;Lamrayah M

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许多自身免疫性疾病,如牛皮癣,导致皮肤成分的改变,通常表现为不想要的局部症状。最广泛认可的牛皮癣样动物模型之一是咪喹莫特(IMQ)诱导的小鼠模型。这种表现模拟了复杂皮肤病理的各个方面,可以适用于测试局部治疗方案。我们通过评估文献中未完全描述的一些参数,即对皮肤破坏的精确描述,对该模型进行了彻底的表征。通过经皮失水测量和角化细胞过度增生引起的表皮肿胀分析来评估。免疫染色显示真皮新生血管和血管扩张的程度。此外,我们通过细胞因子水平、脾脏肿胀和引流淋巴结生发中心的出现来研究全身性炎症。所有参数的严重程度与皮肤样品中的IMQ浓度相关。本研究概述了对评估该模型有用的新参数。我们强调皮肤屏障的破坏,并报告在脾脏和淋巴结远处发生的全身性炎症反应。这些新发现的生物学终点可以用来研究银屑病和其他几种皮肤炎症性疾病的治疗候选药物的疗效。
Many autoimmune disorders such as psoriasis lead to the alteration of skin components which generally manifests as unwanted topical symptoms. One of the most widely approved psoriasis-like animal models is the imiquimod (IMQ)-induced mouse model. This representation mimics various aspects of the complex cutaneous pathology and could be appropriate for testing topical treatment options. We perform a thorough characterization of this model by assessing some parameters that are not fully described in the literature, namely a precise description of skin disruption. It was evaluated by transepidermal water loss measurements and analyses of epidermis swelling as a consequence of keratinocyte hyperproliferation. The extent of neo-angiogenesis and hypervascularity in dermis were highlighted by immunostaining. Moreover, we investigated systemic inflammation through cytokines levels, spleen swelling and germinal centers appearance in draining lymph nodes. The severity of all parameters was correlated to IMQ concentration in skin samples. This study outlines new parameters of interest useful to assess this model. We highlight the skin barrier disruption and report a systemic inflammatory reaction occurring at distance both in spleen and lymph nodes. These newly identified biological endpoints could be exploited to investigate the efficacy of therapeutic candidates for psoriasis and more extensively for several other skin inflammatory diseases.
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