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.
Körholz
D
D
Department of Paediatric Haematology and Oncology, Heinrich-Heine University Medical Centre, Düsseldorf, Germany.
Nussbaum
P
P
Pafferath
B
B
Mauz-Körholz
C
C
Hempel
L
L
Burdach
S
S
D001402:B-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D004789:Enzyme Activation / Q000276:immunology; D006801:Humans; D016133:Polymerase Chain Reaction; D011493:Protein Kinase C / Q000502:physiology*; D012333:RNA, Messenger / Q000097:blood; D018123:Receptors, Interleukin / Q000096:biosynthesis* / Q000737:chemistry; D019947:Receptors, Interleukin-6; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D012333:RNA, Messenger; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate