| First Author | Kimura A | Year | 2004 |
| Journal | J Biol Chem | Volume | 279 |
| Issue | 8 | Pages | 6905-10 |
| PubMed ID | 14699146 | Mgi Jnum | J:88961 |
| Mgi Id | MGI:3037512 | Doi | 10.1074/jbc.C300496200 |
| Citation | Kimura A, et al. (2004) SOCS3 is a physiological negative regulator for granulopoiesis and granulocyte colony-stimulating factor receptor signaling. J Biol Chem 279(8):6905-10 |
| abstractText | The suppressor of cytokine signaling-3 (SOCS3/CIS3) has been shown to be an important negative regulator of cytokines, especially cytokines that activate STAT3. To examine the role of SOCS3 in neutrophils and the granulocyte colony-stimulating factor (G-CSF) signaling in vivo, we compared neutrophils from two types of conditional knockout mice, LysM-Cre:SOCS3(fl/fl) mice and Tie2-Cre:SOCS3(fl/fl) mice, in which the Socs3 gene had been deleted in mature neutrophils and hematopoietic stem cells, respectively. The size of the G-CSF-dependent colonies from Tie2-Cre:SOCS3(fl/fl) mouse bone marrow was much larger than that of colonies from control wild-type mice, while the size of interleukin-3-dependent colonies was similar. Moreover, LysM-Cre:SOCS3(fl/fl) mice had more neutrophils than SOCS3(fl/fl) mice, suggesting that SOCS3 is a negative regulator of G-CSF signaling in neutrophils. Consistent with this notion, G-CSF-induced STAT3 as well as mitogen-activated protein kinase activation was much stronger and prolonged in SOCS3-deficient mature neutrophils than in wild-type neutrophils. The preventive effect of G-CSF on apoptosis was more prominent in SOCS3-deficient mature neutrophils than in control neutrophils. These data indicate that SOCS3 negatively regulates granulopoiesis and G-CSF signaling in neutrophils and may contribute to neutrophilia or neutropenia. |
