Debets R, Hegmans J P, Deleuran M, Hooft S, Benner R, Prens E P
Department of Immunology, Erasmus University Rotterdam, Netherlands.
Cytokine. 1996 Jan;8(1):70-9. doi: 10.1006/cyto.1996.0010.
Interleukin(IL-)6 is overproduced in psoriatic lesions. We investigated the contribution of dermal fibroblasts to the local IL-6 production. Fibroblasts (passageno. 2 to 6) derived from lesional psoriatic (PP) and normal human (NN) skin were used to analyse the secretion of IL-6, and the related cytokines IL-1, IL-8 and TNF-alpha, and the expression of their corresponding mRNA by bioassay, ELISA and Northern hybridization, respectively. PP fibroblasts cultured under serum-free conditions produced increased amounts of bioactive IL-6 when compared to NN fibroblasts. Differences were partially restored in the presence of growth factors or serum. The serum-induced IL-6 production reached a maximum within 24 h after seeding and remained unchanged in PP fibroblasts, whereas comparable amounts of IL-6 were produced only 6 days later in NN fibroblasts. There was a clear expression of IL-6 mRNA in both types of fibroblasts under serum-free conditions. Unexpectedly, fetal calf serum, inactivated fetal calf serum as well as human serum completely inhibited the expression of IL-6 mRNA in all the PP fibroblast cultures investigated. NN fibroblasts were clearly less sensitive to this inhibiting effect of serum. Furthermore, medium supplemented with serum-free component or calcium also repressed IL-6 mRNA expression in PP fibroblasts in contrast to NN fibroblasts. Cycloheximide fully restored the repressing effect of serum indicating that serum induced a labile repressor protein. PP and NN fibroblasts produced negligible amounts of IL-1 and TNF-alpha, but the production of IL-8, however, was comparable to that of IL-6. Our results show a differently regulated IL-6 synthesis in PP fibroblasts in vitro, suggesting an active contribution of dermal fibroblasts to the local IL-6 production in psoriasis.
白细胞介素（IL-）6在银屑病皮损中过度产生。我们研究了真皮成纤维细胞对局部IL-6产生的作用。使用来自银屑病皮损（PP）和正常人皮肤（NN）的成纤维细胞（传代次数2至6），分别通过生物测定、酶联免疫吸附测定（ELISA）和Northern杂交分析IL-6、相关细胞因子IL-1、IL-8和肿瘤坏死因子-α（TNF-α）的分泌及其相应mRNA的表达。与NN成纤维细胞相比，在无血清条件下培养的PP成纤维细胞产生的生物活性IL-6量增加。在生长因子或血清存在的情况下，差异部分恢复。血清诱导的IL-6产生在接种后24小时内达到最大值，并且在PP成纤维细胞中保持不变，而在NN成纤维细胞中仅在6天后才产生相当量的IL-6。在无血清条件下，两种类型的成纤维细胞中均有明显的IL-6 mRNA表达。出乎意料的是，胎牛血清、灭活胎牛血清以及人血清在所有研究的PP成纤维细胞培养物中完全抑制了IL-6 mRNA的表达。NN成纤维细胞对血清的这种抑制作用明显不敏感。此外，与NN成纤维细胞相比，补充无血清成分或钙的培养基也抑制了PP成纤维细胞中IL-6 mRNA的表达。放线菌酮完全恢复了血清的抑制作用，表明血清诱导了一种不稳定的阻遏蛋白。PP和NN成纤维细胞产生的IL-1和TNF-α量可忽略不计，但IL-8的产生与IL-6相当。我们的结果表明，体外PP成纤维细胞中IL-6的合成调节不同，提示真皮成纤维细胞对银屑病局部IL-6的产生有积极作用。
