Wang Frank, Lee Edmund, Lowes Michelle A, Haider Asifa S, Fuentes-Duculan Judilyn, Abello Maria Veronica, Chamian Francesca, Cardinale Irma, Krueger James G
Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York 10021, USA.
J Invest Dermatol. 2006 Jul;126(7):1590-9. doi: 10.1038/sj.jid.5700310. Epub 2006 Apr 27.
We assessed expression of IL-20 and its receptors in psoriasis, given the recent implication of IL-20 in epidermal hyperplasia. Psoriatic lesional (LS) skin consistently expressed more IL-20 mRNA than nonlesional (NL) skin. Immunoreactivity to IL-20 protein was greater in LS tissue and mainly localized to infiltrating CD68+/CD11c+ (myeloid-derived) dermal leukocytes. Because this contrasted with earlier reports of a keratinocyte source, we assessed IL-20 mRNA expression in a variety of cells in vitro, and confirmed a myeloid-derived cellular source (monocytes). Plastic adhesion, activation of beta2 integrins, and incubation with tumor necrosis factor-alpha stimulated expression in these cells. IL-20 receptor (IL-20R)alpha and IL-20Rbeta mRNA was decreased in LS versus NL skin, which also contrasted with earlier findings. To investigate the relationship between IL-20 and disease activity, we examined psoriasis patients treated with the CD2-targeted agent alefacept. In therapeutic responders, lesional IL-20 mRNA decreased to NL levels, suggesting that CD2+ leukocytes may proximally regulate IL-20. Finally, to assess IL-20 function, we used microarrays to screen IL-20-treated keratinocytes, which demonstrated upregulation of disease-related and IFN-gamma-induced genes. Hence, IL-20 may influence inflammation through IFN-like effects. Together, these data indicate that IL-20 may be an important effector cytokine in psoriasis, and that its inhibition may represent a potential therapeutic target.
鉴于白细胞介素-20（IL-20）最近被认为与表皮增生有关，我们评估了其在银屑病中的表达情况。银屑病皮损（LS）皮肤中IL-20 mRNA的表达始终高于非皮损（NL）皮肤。LS组织中对IL-20蛋白的免疫反应性更强，且主要定位于浸润的CD68+/CD11c+（髓系来源）真皮白细胞。由于这与早期关于角质形成细胞来源的报道相反，我们在体外评估了多种细胞中IL-20 mRNA的表达，并证实其来源于髓系细胞（单核细胞）。这些细胞的塑料黏附、β2整合素的激活以及与肿瘤坏死因子-α的孵育刺激了其表达。与NL皮肤相比，LS皮肤中IL-20受体（IL-20R）α和IL-20Rβ mRNA水平降低，这也与早期研究结果不同。为了研究IL-20与疾病活动之间的关系，我们检查了接受靶向CD2药物阿法赛特治疗的银屑病患者。在治疗有反应者中，皮损处IL-20 mRNA降至NL水平，提示CD2+白细胞可能在近端调节IL-20。最后，为了评估IL-20的功能，我们使用微阵列筛选了经IL-20处理的角质形成细胞，结果显示与疾病相关的基因和干扰素-γ诱导的基因上调。因此，IL-20可能通过类似干扰素的作用影响炎症。总之，这些数据表明IL-20可能是银屑病中一种重要的效应细胞因子，抑制它可能是一个潜在的治疗靶点。
