Matsumiya T, Imaizumi T, Fujimoto K, Cui X, Shibata T, Tamo W, Kumagai M, Tanji K, Yoshida H, Kimura H, Satoh K
Department of Dentistry and Oral Surgery, Hirosaki University School of Medicine, Hirosaki, 036-8562, Japan.
Exp Cell Res. 2001 Sep 10;269(1):35-41. doi: 10.1006/excr.2001.5300.
Soluble form of IL-6 receptor alpha (sIL-6R) is known to serve as an agonist, without exogenous IL-6, on endothelial cells which do not express IL-6R but have only IL-6 receptor beta chain, gp130. We investigated the effect of sIL-6R on fractalkine expression in human umbilical vein endothelial cells (HUVECs) in culture. sIL-6R markedly inhibited HUVEC fractalkine/CX3CL1 expression induced by interleukin (IL)-1alpha, tumor necrosis factor (TNF)-alpha, or interferon (IFN)-gamma. IL-1alpha-induced fractalkine expression was inhibited by sIL-6R in time- and concentration-dependent manners. The experiment using actinomycin D indicated that sIL-6R lowered the stability of fractalkine mRNA. The inhibitory effect of sIL-6R was reversed by anti-gp130 neutralizing antibody. sIL-6R inhibited adhesion of mononuclear cells (MNCs) to HUVEC monolayers stimulated with IFN-gamma, but it did not inhibit the adhesion to monolayers stimulated with IL-1alpha. MNC chemotactic activity of conditioned medium of HUVEC stimulated with IL-1alpha or IFN-gamma was inhibited by co-treatment with sIL-6R. sIL-6R may play a regulatory role in immune responses by modulating the interaction between leukocytes and the vascular endothelium.
已知白细胞介素-6受体α的可溶性形式（sIL-6R）在不表达IL-6R但仅有IL-6受体β链gp130的内皮细胞上，可作为一种无需外源性IL-6的激动剂。我们研究了sIL-6R对培养的人脐静脉内皮细胞（HUVECs）中趋化因子表达的影响。sIL-6R显著抑制了由白细胞介素（IL）-1α、肿瘤坏死因子（TNF）-α或干扰素（IFN）-γ诱导的HUVEC趋化因子/CX3CL1表达。sIL-6R以时间和浓度依赖性方式抑制IL-1α诱导的趋化因子表达。使用放线菌素D的实验表明，sIL-6R降低了趋化因子mRNA的稳定性。sIL-6R的抑制作用可被抗gp130中和抗体逆转。sIL-6R抑制单核细胞（MNCs）与经IFN-γ刺激的HUVEC单层的黏附，但不抑制与经IL-1α刺激的单层的黏附。与sIL-6R共同处理可抑制经IL-1α或IFN-γ刺激的HUVEC条件培养基的MNC趋化活性。sIL-6R可能通过调节白细胞与血管内皮之间的相互作用在免疫反应中发挥调节作用。
