ACTIVATION OF JUNB AND C-MYC PRIMARY RESPONSE GENES BY INTERLEUKIN-9 IN A HUMAN FACTOR-DEPENDENT CELL-LINE

Interleukin 9 (IL-9) stimulates the proliferation of various hematopoi etic cell types. To elucidate the molecular mechanisms underlying the cell proliferation action, immediate-early gene expression elicited by IL-9 in a human factor-dependent cell line, MO7e, was studied. IL-9 s timulation resulted in a rapid and transient elevation of primary resp onse genes including junB and c-myc. The differential effects of prote in kinase inhibitors, herbimycin A, genistein, and H-7 on the steady-s tate mRNA level and the transcription rate of junB and c-myc genes tri ggered by IL-9 were also investigated. Herbimycin A, but not genistein , specifically inhibited the expression of junB steady-state mRNA and the in vitro transcription of the junB gene. IL-9-enhanced c-myc gene expression was completely inhibited by both herbimycin A and genistein at the level of transcriptional initiation. H-7 failed to inhibit c-m yc, but partially abolished junB mRNA induction. The role of protein k inase C in IL-9-mediated junB induction was also examined. The differe nt responses of junB and c-myc messages to protein kinase inhibitors s uggested that more than one pathway may be involved in IL-9-mediated s ignal transduction which leads to the expression of junB and c-myc gen es. (C) 1995 Wiley-Liss, Inc.