PDF(Pubmed)
Abstract：
SOCS are a family of negative inhibitors of the molecular cascades induced by cytokines, growth factors and hormones. At molecular level, SOCS proteins inhibit the kinase activity of specific sets of receptor-associated Janus Activated Kinases (JAKs), thereby suppressing the propagation of intracellular signals. Of the eight known members, SOCS1 and SOCS3 inhibit activity of JAKs mainly induced by cytokines and can play key roles in regulation of inflammatory and immune responses. SOCS1 and SOCS3 are the most well-characterized SOCS members in skin inflammatory diseases, where their inhibitory activity on cytokine activated JAKs and consequent anti-inflammatory action has been widely investigated in epidermal keratinocytes. Structurally, SOCS1 and SOCS3 share the presence of a N-terminal domain containing a kinase inhibitory region (KIR) motif able to act as a pseudo-substrate for JAK and to inhibit its activity. During the last decades, the design and employment of SOCS1 and SOCS3-derived peptides mimicking KIR domains in experimental models of dermatoses definitively established a strong anti-inflammatory and ameliorative impact of JAK inhibition on skin inflammatory responses. Herein, we discuss the importance of the findings collected in the past on SOCS1 and SOCS3 function in the inflammatory responses associated to skin immune-mediated diseases and malignancies, for the development of the JAK inhibitor drugs. Among them, different JAK inhibitors have been introduced in the clinical practice for treatment of atopic dermatitis and psoriasis, and others are being investigated for skin diseases like alopecia areata and vitiligo.
摘要：
SOCS是细胞因子诱导的分子级联反应的负抑制剂家族，生长因子和激素。在分子水平上,SOCS蛋白抑制特定组的受体相关Janus活化激酶（JAK）的激酶活性，从而抑制细胞内信号的传播。在已知的八个成员中，SOCS1和SOCS3抑制主要由细胞因子诱导的JAK活性,在炎症和免疫反应的调节中发挥关键作用。SOCS1和SOCS3是皮肤炎症性疾病中特征最明确的SOCS成员，在表皮角质形成细胞中广泛研究了它们对细胞因子激活的JAK的抑制活性和随后的抗炎作用。在结构上,SOCS1和SOCS3共有一个N末端结构域，该结构域含有激酶抑制区（KIR）基序，该基序能够充当JAK的假底物并抑制其活性。在过去的几十年里，在皮肤病实验模型中模拟KIR结构域的SOCS1和SOCS3衍生肽的设计和使用,最终确立了JAK抑制对皮肤炎症反应的强抗炎和改善作用.在这里，我们讨论了过去收集的关于SOCS1和SOCS3在与皮肤免疫介导的疾病和恶性肿瘤相关的炎症反应中的作用的重要性。用于开发JAK抑制剂药物。其中,不同的JAK抑制剂已经在临床实践中被引入治疗特应性皮炎和银屑病,和其他人正在调查皮肤疾病，如斑秃和白癜风。
