Induction of Bv8 Expression by Granulocyte Colony-stimulating Factor in CD11b+Gr1+ Cells KEY ROLE OF Stat3 SIGNALING

摘要: Bv8, also known as prokineticin 2, has been characterized an important mediator of myeloid cell mobilization and cell-dependent tumor angiogenesis. Bv8 expression is dramatically enhanced by G-CSF, both in vitro vivo. The mechanisms involved such up-regulation remain unknown. Using pharmacological inhibitors that interfere with multiple signaling pathways to be activated we show signal transducer activator transcription 3 (Stat3) activation required for mouse bone marrow cells, whereas other Stat family members extracellular signal-regulated kinase (ERK) are not involved. We further identified CD11b+ Gr1+ cells the primary population which Stat3 G-CSF. induced G-CSF was significantly reduced siRNA-mediated knockdown. Moreover, chromatin immunoprecipitation studies indicate induces binding phospho-Stat3 promoter, abolished pretreatment inhibitor WP1066. Luciferase assay confirmed site a functional enhancer promoter. key role regulating G-CSF-induced vivo studies. regulation human signaling-dependent. recognized regulator inflammation-dependent tumorigenesis. propose reflects at least part its ability regulate expression.