Neutrophil Elastase Regulates Emergency Myelopoiesis Preceding Systemic Inflammation in Diet-induced Obesity
Neutrophil Elastase Regulates Emergency Myelopoiesis Preceding Systemic Inflammation in Diet-induced Obesity
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DOI：
10.1074/jbc.c116.758748
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发表时间：
2017-03-24
影响因子：
4.8
通讯作者：
Jiang, Zhen Y.
中科院分区：
文献类型：
--
作者：
Huang, Jun-Yuan;Zhou, Qiong Lin;Jiang, Zhen Y.
Inflammation plays a significant role in the development of obesity-related complications, but the molecular events that initiate and propagate such inflammation remain unclear. Here, we report that mice fed a high fat diet (HFD) for as little as 1-3 days show increased differentiation of myeloid progenitors into neutrophils and monocytes but reduced B lymphocyte production in the bone marrow. Levels of neutrophil elastase (NE) and the nuclear factors CCAAT/ enhancer-binding protein alpha (C/ EBP alpha) and growth factor-independent 1 (GFI-1) are elevated in hematopoietic stem and progenitor cells from HFD-fed mice, but mice lacking either NE or C/EBP alpha are resistant to HFDinduced myelopoiesis. NE deletion increases expression of the inhibitory isoform of p30 C/EBP alpha, impairs the transcriptional activity of p42 C/EBP alpha, and reduces expression of the C/EBP alpha target gene GFI-1 in hematopoietic stem and progenitor cells, suggesting a mechanism by which NE regulates myelopoiesis. Furthermore, NE deletion prevents HFD-induced vascular leakage. Thus, HFD feeding rapidly activates bone marrow myelo-poiesis through the NE-dependent C/EBP alpha-GFI-1 pathway preceding vascular damage and systemic inflammation.
