抄録
Megakaryopoiesis is associated with inflammation, and certain inflammatory cytokines stimulate hematopoietic progenitors to differentiate into megakaryocytes. Interferon-γ ( IFN-γ) is an inflammatory cytokine that stimulates megakaryocyte development, and interferon regulatory factors (IRFs), IRF-1 and IRF-2 are typical transcription factors that are involved in the IFN-γ response. We investigate the role of IRFs in megakaryopoiesis. Mouse bone marrow hematopoietic stem cells (HSCs) were prepared and stimulated with IFN-γ. IFN-γ treatment induced IRF-2 expression as well as that of CD41 although induction levels of both were much lower than those of IRF-1. When IRF expression levels were studied in mouse bone marrow cell fractions, IRF-2 expression was relatively high in HSCs. An in vitro clonogenic assay showed that IRF-2 overexpressed cells increased the number of megakaryocytic colonies, but IRF-1 overexpressed cells did not, suggesting that IRF-2 is involved in megakaryopoiesis. Mechanistic analysis showed that IRF-2 transfection up-regulated CD41 promoter activity in hematopoietic cell lines through its binding to an ISRE-like site in the CD41 promoter. These findings suggest that IRF-2 plays an important role in megakaryocytic cell commitment or differentiation from HSCs by regulating CD41 expression under inflammation conditions.
