Körholz D, Nussbaum P, Pafferath B, Mauz-Körholz C, Hempel L, Burdach S
Department of Paediatric Haematology and Oncology, Heinrich-Heine University Medical Centre, Düsseldorf, Germany.
Scand J Immunol. 1994 Nov;40(5):515-20. doi: 10.1111/j.1365-3083.1994.tb03498.x.
The mechanism of protein kinase C (PKC) induced release of the soluble interleukin-6 receptor (sIL-6R) from human B cells was investigated. Phorbol myristat acetat (PMA)-induced activation of PKC significantly enhanced the release of sIL-6R from the human B-cell line SKW 6.4. The PMA effect was completely blocked by cycloheximide, whereas different inhibitors of proteases had no effect. In contrast to the effect on sIL-6R release, FACS analysis did not reveal any effect of PMA on the expression of IL-6R on the surface of SKW 6.4 cells. After 6 h of stimulation with PMA, analysis of mRNA expression using a polymerase chain reaction-(PCR)-assisted mRNA amplification assay, showed increased expression of a spliced mRNA encoding for a soluble form of IL-6R. Comparable to the results in SKW 6.4 cells, activation of purified human B cells with PMA induced a significant augmentation of sIL-6R release which was also sensitive to cycloheximide. In conclusion, a novel mechanism of sIL-6R release is reported involving de novo synthesis. Thus, sIL-6R release from human B cells is completely different compared with that described in hepatocytes, which involved rapid, proteolytic cleavage of the membrane-bound receptor but not de novo synthesis. The results of this study may help to understand the molecular control of sIL-6R release from human B cells.
研究了蛋白激酶C（PKC）诱导人B细胞释放可溶性白细胞介素-6受体（sIL-6R）的机制。佛波醇肉豆蔻酸酯乙酸酯（PMA）诱导的PKC激活显著增强了人B细胞系SKW 6.4中sIL-6R的释放。PMA的作用被放线菌酮完全阻断，而不同的蛋白酶抑制剂则没有作用。与对sIL-6R释放的影响相反，流式细胞术分析未显示PMA对SKW 6.4细胞表面IL-6R表达有任何影响。用PMA刺激6小时后，使用聚合酶链反应（PCR）辅助的mRNA扩增试验分析mRNA表达，结果显示编码可溶性IL-6R形式的剪接mRNA表达增加。与SKW 6.4细胞中的结果相似，用PMA激活纯化的人B细胞可显著增加sIL-6R的释放，且该释放对放线菌酮也敏感。总之，报道了一种涉及从头合成的sIL-6R释放新机制。因此，人B细胞中sIL-6R的释放与肝细胞中描述的完全不同，肝细胞中涉及膜结合受体的快速蛋白水解切割，而不是从头合成。本研究结果可能有助于理解人B细胞中sIL-6R释放的分子调控。
