Brunner Patrick M, Glitzner Elisabeth, Reininger Baerbel, Klein Irene, Stary Georg, Mildner Michael, Uhrin Pavel, Sibilia Maria, Stingl Georg
Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Exp Dermatol. 2015 Jul;24(7):522-8. doi: 10.1111/exd.12709. Epub 2015 May 4.
Chemokines are small chemotactic proteins that have a crucial role in leukocyte recruitment into tissue. Targeting these mediators has been suggested as a potential therapeutic option in inflammatory skin diseases such as psoriasis. Using quantitative RT-PCR, we found CCL7, a chemokine ligand known to interact with multiple C-C chemokine receptors, to be markedly increased in lesional psoriasis as opposed to atopic dermatitis, lichen planus, non-lesional psoriatic and normal control skin. Surprisingly, this increase in CCL7 mRNA expression exceeded that of all other chemokines investigated, and keratinocytes and dermal blood endothelial cells were identified as its likely cellular sources. In an imiquimod-induced psoriasis-like mouse model, CCL7 had a profound impact on myeloid cell inflammation as well as on the upregulation of key pro-psoriatic cytokines such as CCL20, IL-12p40 and IL-17C, while its blockade led to an increase in the antipsoriatic cytokine IL-4. In humans receiving the TNF-α-blocker infliximab, CCL7 was downregulated in lesional psoriatic skin already within 16 hours after a single intravenous infusion. These data suggest that CCL7 acts as a driver of TNF-α-dependent Th1/Th17-mediated inflammation in lesional psoriatic skin.
趋化因子是一类小分子趋化蛋白，在白细胞募集到组织中发挥关键作用。针对这些介质已被提议作为治疗银屑病等炎症性皮肤病的潜在治疗选择。通过定量逆转录聚合酶链反应（RT-PCR），我们发现CCL7，一种已知与多种C-C趋化因子受体相互作用的趋化因子配体，在银屑病皮损中相对于特应性皮炎、扁平苔藓、非皮损性银屑病和正常对照皮肤显著增加。令人惊讶的是，CCL7信使核糖核酸（mRNA）表达的增加超过了所有其他研究的趋化因子，并且角质形成细胞和真皮血管内皮细胞被确定为其可能的细胞来源。在咪喹莫特诱导的银屑病样小鼠模型中，CCL7对髓样细胞炎症以及关键的促银屑病细胞因子如CCL20、白细胞介素（IL）-12p40和IL-17C的上调有深远影响，而其阻断导致抗银屑病细胞因子IL-4增加。在接受肿瘤坏死因子（TNF）-α阻滞剂英夫利昔单抗的人类中，单次静脉输注后16小时内，皮损性银屑病皮肤中的CCL7就被下调。这些数据表明CCL7在皮损性银屑病皮肤中作为TNF-α依赖性Th1/Th17介导的炎症的驱动因子起作用。
