Neutrophils induce macrophage anti-inflammatory reprogramming by suppressing NF-κB activation.
Neutrophils induce macrophage anti-inflammatory reprogramming by suppressing NF-κB activation.
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DOI：
10.1038/s41419-018-0710-y
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发表时间：
2018-06-04
影响因子：
9
通讯作者：
Hirani N
中科院分区：
文献类型：
--
作者：
Marwick JA;Mills R;Kay O;Michail K;Stephen J;Rossi AG;Dransfield I;Hirani N
凋亡细胞调节巨噬细胞的功能以控制和解决炎症。在这里，我们表明，中性粒细胞诱导快速和持续的抑制NF-κB信号在巨噬细胞通过一个独特的调节关系，这是独立的凋亡。巨噬细胞NF-κB活化的降低通过阻断转化生长因子β激活激酶1（TAK 1）和IKKβ活化而发生。因此，NF-κB B（p65）磷酸化减少，其向细胞核的转运受到抑制，NF-κ B介导的炎性细胞因子转录受到抑制。基因集富集分析表明，NF-κB活化的这种抑制不仅限于经典NF-κB途径的翻译后修饰，而且还在转录水平上印迹。因此，嗜中性粒细胞发挥巨噬细胞的持续抗炎表型重编程，这通过巨噬细胞释放促炎细胞因子而非抗炎细胞因子的持续减少来反映。总之，我们的研究结果确定了一种新的独立于炎症的机制，中性粒细胞通过该机制调节单核细胞/巨噬细胞的介体分布和重编程，代表了炎症控制的重要节点。
Apoptotic cells modulate the function of macrophages to control and resolve inflammation. Here, we show that neutrophils induce a rapid and sustained suppression of NF-κB signalling in the macrophage through a unique regulatory relationship which is independent of apoptosis. The reduction of macrophage NF-κB activation occurs through a blockade in transforming growth factor β-activated kinase 1 (TAK1) and IKKβ activation. As a consequence, NF-κB (p65) phosphorylation is reduced, its translocation to the nucleus is inhibited and NF-κB-mediated inflammatory cytokine transcription is suppressed. Gene Set Enrichment Analysis reveals that this suppression of NF-κB activation is not restricted to post-translational modifications of the canonical NF-κB pathway, but is also imprinted at the transcriptional level. Thus neutrophils exert a sustained anti-inflammatory phenotypic reprogramming of the macrophage, which is reflected by the sustained reduction in the release of pro- but not anti- inflammatory cytokines from the macrophage. Together, our findings identify a novel apoptosis-independent mechanism by which neutrophils regulate the mediator profile and reprogramming of monocytes/macrophages, representing an important nodal point for inflammatory control.
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影响因子：
11.1
作者：
Rhys HI;Dell'Accio F;Pitzalis C;Moore A;Norling LV;Perretti M
通讯作者：
Perretti M
影响因子：
15.9
作者：
Fadok, VA;Bratton, DL;Henson, PM
通讯作者：
Henson, PM
影响因子：
4.4
作者：
Mattioli, I;Sebald, A;Schmitz, ML
通讯作者：
Schmitz, ML
影响因子：
4.4
作者：
Lucas, Mark;Stuart, Lynda M.;Lacy-Hulbert, Adam
通讯作者：
Lacy-Hulbert, Adam
DOI：
10.1164/rccm.200205-479oc
发表时间：
2003-11-15
影响因子：
24.7
作者：
Gagliardo, R;Chanez, P;Vignola, AM
通讯作者：
Vignola, AM