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. 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.