Activation of Protein Kinase C Induces De Novo Synthesis of the Soluble Interleukin‐6 Receptor in Human B Cells

The mechanism of protein kinase C (PKC) induced release of the soluble interleukin‐6 receptor (sIL‐6R) from human B cells was investigated. Phorbot 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 6h of stimulation with PMA, analysis of mRNA expression using a polymerase chain reaction‐(PCR)‐assisled 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.