Lundqvist E N, Companjen A R, Prens E P, Egelrud T
Department of Dermatology, Umeå University, Sweden.
Eur Cytokine Netw. 1998 Mar;9(1):41-6.
We have recently presented evidence that human plantar stratum corneum and psoriatic scales contain biologically active interleukin-1beta (IL-1beta) which has been activated in a process not involving interleukin-1beta-converting-enzyme. The aim of the present study was to compare this form of native IL-1beta with recombinant mature human IL-1beta as regards activity and the effects of inhibitors. In an assay based on the ability of IL-1 to induce the expression of E-selectin in cultured endothelial cells, the maximal activity of IL-1beta partially purified from plantar stratum corneum and recombinant IL-1beta was approximately the same. The specific activity was slightly higher for recombinant IL-1beta, although this difference was within one order of magnitude. An antibody to IL-1beta caused total inhibition of both forms of IL-1beta with no significant differences in the dose-response curves for the antibody. Immunochemical analyses and experiments with neutralising antibodies specific for IL-1alpha and tumor necrosis factor-alpha (TNF-alpha) verified that the observed activity in the partially purified preparation was due to IL-1beta, and not to IL-1alpha or TNF-alpha. There were no significant differences between the two forms of IL-1beta as regards the inhibitory effects of recombinant IL-1 receptor antagonist. Partially purified IL-1beta from plantar stratum corneum and from psoriatic scales were both highly active in the D10 proliferation assay. This activity could be totally inhibited with an IL-1beta specific antibody. This work thus confirms the presence of biologically active IL-1beta in plantar stratum corneum and psoriatic scales. Alternatively activated IL-1beta in the epidermis should be considered in future studies on skin biology and pathophysiology.
我们最近提供了证据,表明人类足底角质层和银屑病鳞屑中含有生物活性白细胞介素-1β(IL-1β),其在一个不涉及白细胞介素-1β转换酶的过程中被激活。本研究的目的是比较这种天然形式的IL-1β与重组人成熟IL-1β在活性及抑制剂作用方面的差异。在一项基于IL-1诱导培养的内皮细胞中E-选择素表达能力的检测中,从足底角质层部分纯化的IL-1β和重组IL-1β的最大活性大致相同。重组IL-1β的比活性略高,尽管这种差异在一个数量级之内。抗IL-1β抗体可完全抑制两种形式的IL-1β,抗体的剂量反应曲线无显著差异。免疫化学分析以及针对IL-1α和肿瘤坏死因子-α(TNF-α)的中和抗体实验证实,部分纯化制剂中观察到的活性是由IL-1β引起的,而非IL-1α或TNF-α。就重组IL-1受体拮抗剂的抑制作用而言,两种形式的IL-1β之间没有显著差异。从足底角质层和银屑病鳞屑中部分纯化的IL-1β在D10增殖检测中均具有高活性。这种活性可被IL-1β特异性抗体完全抑制。因此,这项工作证实了足底角质层和银屑病鳞屑中存在生物活性IL-1β。在未来关于皮肤生物学和病理生理学的研究中,应考虑表皮中经替代激活的IL-1β。