Interferon Kappa Is Up-Regulated in Psoriasis and It Up-Regulates Psoriasis-Associated Cytokines in vivo
Interferon Kappa Is Up-Regulated in Psoriasis and It Up-Regulates Psoriasis-Associated Cytokines in vivo
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DOI：
10.2147/ccid.s218243
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发表时间：
2019-01-01
影响因子：
2.3
通讯作者：
Deng, Liehua
中科院分区：
文献类型：
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作者：
Li, Yuanyuan;Song, Yueqi;Deng, Liehua
目的：银屑病患者中I型干扰素信号增加。干扰素κ（IFN-κ）是由角质形成细胞组成性表达的I型干扰素家族的成员。在这项研究中，我们调查是否IFN-κ参与银屑病patients and methods：20例健康人，20例寻常型银屑病患者和10例异位性皮炎（AD）被纳入本研究。结果：IFN-κ蛋白在正常皮肤表皮中表达极低，而在银屑病皮损表皮角质形成细胞基底层上表达明显增高。而AD皮损中的表达与正常皮肤相似。此外，在银屑病患者的血清中检测到IFN-kappa蛋白，但在正常受试者和AD的血清中未检测到。我们进一步研究了NHEK中IFNk基因表达的调控。我们发现，在NHEK中，IFNk被核酸病原体识别受体（PRR）激动剂的类型显著诱导。虽然其表达被自身和IFN-γ显著诱导，但其被2型免疫细胞因子IL 4和IL 13抑制;其他炎性细胞因子包括IL 1超家族成员和IL 17 A不改变其表达。添加重组IFN-κ不影响角质形成细胞的分化。使用小鼠实验模型，我们证明皮下注射重组IFN-κ并不增加皮肤厚度，但显著增加TNFA和IL 17 A在小鼠皮肤中的转录。结论：IFN-κ在银屑病中的增加可能是由受损细胞释放核酸、IFN-γ增加和自身激活引起的。其增强可能通过增强TNFA和IL 17 A基因表达而有助于疾病的病因学。
Purpose: There is increased type I interferon signature in psoriasis patients. Interferonkappa (IFN-kappa) is a member of type I interferon family that is constitutively expressed by keratinocytes. In this study, we investigate whether IFN-kappa is involved in psoriasis etiology.Patients and methods: Twenty healthy individuals, 20 psoriasis vulgaris patients and 10 atopic dermatitis (AD) were included for this study. Immunohistochemistry staining, normal human epidermal keratinocytes (NHEK) culture, Ca2Cl-induced differentiation, quantitative reverse transcription (qRT-PCR), ELISA and murine experiments were performed.Results: We found IFN-kappa protein expression was extremely low in the epidermis of normal skin, but it was significantly increased in the suprabasal layers of epidermal keratinocytes in psoriatic skin lesions. However, its expression in the skin lesions of AD was similar to normal skin. Additionally, IFN-kappa protein was detected in sera from psoriasis patients, but not in sera from normal subjects and AD. We further investigated the regulation of IFNk gene expression in NHEK. We found that IFNk was significantly induced by types of nucleic acid pathogen recognition receptor (PRR) agonists in NHEK. While its expression was significantly induced by itself and IFN-gamma, it was inhibited by type 2 immunity cytokines IL4 and IL13; other inflammatory cytokines including IL1 super-family members and IL17A did not alter its expression. Addition of recombinant IFN-kappa did not affect keratinocytes differentiation. Using the murine experimental model, we demonstrated that subcutaneous administration of recombinant IFN-kappa did not increase skin thickness, but significantly increased the transcription of TNFA and IL17A in mice skin.Conclusion: Increased IFN-kappa in psoriasis may be caused by injured cells-released nucleic acids, increased IFN-gamma and self-activation. Its enhancement may contribute to the etiology of the disease by enhancing TNFA and IL17A gene expression.