| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
In CD34 positive hematopoietic progenitor cells, stem cell factor(SCF), granulocyte colony-stimulating factor(G-CSF), thrombopoietin(TPO), granulocyte-macrophage colony-stimulating factor(GM-CSF), interleukin(IL)-3, and tumor necrosis factor(TNF)-α mediated phosphorylation of extracellular-signal regulated kinase(ERK), IL-1 and TNF-α mediated phosphorylation of p38 MAP kinase, TNF-α mediated phosphorylation of c-Jun N-terminal kinase (JNK). Inhibitors of p38 MAP kinase inhibited expression of CD11b and CD15 induced by IL-1b. IL-6/sIL-6R,G-CSF,TPO,GM-CSF,IL-3,IFN-α, and IFN-γ mediated phosphorylation of signal transducer and activator of transcription(STAT)3-Y,SCF,IL-6/sIL-6R,G-CSF,TPO,GM-CSF,IL-3, and TNF-α mediated phosphorylation of STST3-S,G-CSF,TPO,GM-CSF, IL-3, and IFN-a mediated phosphorylation of STST5a,G-CSF,GM-CSF,IL-3,IFN-α, and IFN-γ mediated phosphorylation of STAT5b, and IFN-α and IFN-γ mediated phosphorylation of STAT 1.
Mature human neutrophils with normal functions (chemotaxis, phagocytosis and superoxide release) were ex vivo expanded from haematopoietic progenitor cells as the following procedure. CD34 positive haematopoietic progenitor cells were cultivated with SCF,IL-3,GM-CSF, and G-CSF for 7 days, and thereafter non-adherent cells were further cultivated for 7 days with G-CSF alone. TPO stimulated ex vivo expansion of mature neutrophils in the early stages of differentiation. Human neutrophils were expressed members of the inhibitor of apoptosis (LAP) family (cIAP1,cIAP2, and X-linked LAP). G-CSF selectively up-regulated c-IAP2 expression. A specific inhibitor of Janus kinase 2(JAK2) inhibited G-CSF-induced up-regulation of cIAP2, phosphorylation of STAT3, and the antiapoptotic effects. In monocyte, G-CSF inhibited LPS-induced TNF-α production and activated STST3. These effects were prevented by an inhibitor of JAK2.
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