Possible new role for NF-κB in the resolution of inflammation
Possible new role for NF-κB in the resolution of inflammation
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DOI：
10.1038/nm1201-1291
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发表时间：
2001-12-01
期刊：
影响因子：
82.9
通讯作者：
Willoughby, DA
中科院分区：
文献类型：
--
作者：
Lawrence, T;Gilroy, DW;Willoughby, DA
炎症涉及信号通路的连续激活，导致促炎介质和抗炎介质的产生。尽管人们的注意力集中在引发炎症的促炎途径上，但人们对关闭炎症和解决炎症反应的机制知之甚少。转录因子 NF-kappaB 被认为在诱导促炎基因表达中起核心作用，并作为治疗炎症疾病的新靶点引起了人们的兴趣。我们在此表明，炎症发作期间募集的白细胞中 NF-κB 的激活与促炎基因表达相关，而炎症消退期间的这种激活与抗炎基因的表达和细胞凋亡的诱导相关。在炎症消退过程中抑制 NF-κB 可延长炎症反应并防止细胞凋亡。这表明 NF-κB 在体内具有抗炎作用，涉及炎症消退的调节。
Inflammation involves the sequential activation of signaling pathways leading to the production of both pro- and anti-inflammatory mediators. Although much attention has focused on pro-inflammatory pathways that initiate inflammation, relatively little is known about the mechanisms that switch off inflammation and resolve the inflammatory response. The transcription factor NF-kappaB is thought to have a central role in the induction of pro-inflammatory gene expression and has attracted interest as a new target for the treatment of inflammatory disease. We, show here that NF-kappaB activation in leukocytes recruited during the onset of inflammation is associated with pro-inflammatory gene expression, whereas such activation during the resolution of inflammation is associated with the expression of anti-inflammatory genes and the induction of apoptosis. Inhibition of NF-kappaB during the resolution of inflammation protracts the inflammatory response and prevents apoptosis. This:suggests that NF-kappaB has an anti-inflammatory role in vivo involving the regulation of inflammatory resolution.