Enhancement of interleukin-3-dependent mast cell proliferation by suppression of c-jun expression.
We have previously shown that protein kinase C (PKC) depletion is associated with an increase in the proliferation of interleukin 3 (IL-3)-induced mast cells. Here we show that the AP-1 components c-Jun and c-Fos are induced by IL-3. While c-Jun's induction by IL-3 is totally dependent on PKC, c-Fos induction by IL-3 is only attenuated by PKC depletion. AP-1 binding activity was also induced by IL-3 but this induction was PKC independent. These results indicated a possible involvement of c-Jun in the inhibition of IL-3-induced growth regulation. A support for this assumption came from experiments in which an increase in thymidine incorporation into mast cells was noted when c-jun antisense oligomers were administered to IL-3-treated cells. Since the only known effect of direct inhibition of c-Jun on proliferation rates in several cellular systems was a reduction of proliferation, we verified that our c-jun antisense oligomer could also inhibit proliferation rates in fibroblasts where such a repression was previously reported. Thus c-Jun has an inhibitory effect on IL-3 induction of mast cells proliferation that is distinct from its role in several other cellular environments. These observations reveal the involvement of AP-1 and its components in IL-3-induced signal transduction and the importance of the mast cell environment in determining their specific cellular function.
Chaikin
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E
Institute of Biochemistry, Hebrew University, Hadassah Medical School, Jerusalem, Israel.
Hakeem
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I
Razin
E
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D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis; D017931:DNA Primers; D015342:DNA Probes; D015870:Gene Expression / Q000187:drug effects*; D016758:Genes, jun / Q000187:drug effects; D007377:Interleukin-3 / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000302:isolation & purification; D016755:Proto-Oncogene Proteins c-jun / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000302:isolation & purification; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism
D017931:DNA Primers; D015342:DNA Probes; D007377:Interleukin-3; D016376:Oligonucleotides, Antisense; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D004247:DNA; D011493:Protein Kinase C; D013936:Thymidine