15-epi-Lipoxin A(4), Resolvin D2, and Resolvin D3 Induce NF-κB Regulators in Bacterial Pneumonia.
15-epi-Lipoxin A(4), Resolvin D2, and Resolvin D3 Induce NF-κB Regulators in Bacterial Pneumonia.
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DOI：
10.4049/jimmunol.1602090
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发表时间：
2018-04-15
期刊：
影响因子：
--
通讯作者：
Levy BD
中科院分区：
文献类型：
--
作者：
Sham HP;Walker KH;Abdulnour RE;Krishnamoorthy N;Douda DN;Norris PC;Barkas I;Benito-Figueroa S;Colby JK;Serhan CN;Levy BD
特异性促消退介质（SPM）可降低NF-κB活性，以防止过度组织损伤并促进急性炎症消退。SPM对NF-κB的调节机制仍有待确定。在此，在LPS攻击后，SPM 15-epi-lipoxin A4（15-epi-LXA 4）、Resolvin D1、Resolvin D2、Resolvin D3和17-epi-RvD 1在鼠肺中体内产生。在LPS激活的人支气管上皮细胞中，选择SPM增加NF-κB调节因子A20和SIGIRR的表达。令人感兴趣的是，15-epi-LXA 4在上皮细胞和鼠肺炎中以ALX/FPR 2受体依赖性方式诱导A20和SIGIRR。该SPM调节NF-κ B诱导的细胞因子以减少病原体介导的炎症。除了抑制肺部炎症之外，15-表-LXA 4还令人惊讶地增强病原体清除，同时增加抗微生物肽表达。总之，这些结果首次鉴定了A20和SIGIRR表达的内源性激动剂，以调节NF-κB活性，并建立了SPM调节NF-κB以缓解肺炎的机制。
Specialized Pro-resolving Mediators (SPMs) decrease NF-κB activity to prevent excessive tissue damage and promote the resolution of acute inflammation. Mechanisms for NF-κB regulation by SPMs remain to be determined. Here, after LPS challenge, the SPMs 15-epi-lipoxin A4 (15-epi-LXA4), Resolvin D1, Resolvin D2, Resolvin D3 and 17-epi-RvD1 were produced in vivo in murine lung. In LPS-activated human bronchial epithelial cells, select SPMs increased expression of the NF-κB regulators A20 and SIGIRR. Of interest, 15-epi-LXA4 induced A20 and SIGIRR in an ALX/FPR2 receptor dependent manner in epithelial cells and in murine pneumonia. This SPM regulated NF-κB-induced cytokines to decrease pathogen-mediated inflammation. In addition to dampening lung inflammation, 15-epi-LXA4 surprisingly also enhanced pathogen clearance with increased antimicrobial peptide expression. Together, these results are the first to identify endogenous agonists for A20 and SIGIRR expression to regulate NF-κB activity and to establish mechanisms for NF-κB regulation by SPMs for pneumonia resolution.
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影响因子：
64.8
作者：
Chiang, Nan;Fredman, Gabrielle;Backhed, Fredrik;Oh, Sungwhan F.;Vickery, Thad;Schmidt, Birgitta A.;Serhan, Charles N.
通讯作者：
Serhan, Charles N.
影响因子：
4.8
作者：
Croasdell, Amanda;Sime, Patricia J.;Phipps, Richard P.
通讯作者：
Phipps, Richard P.
DOI：
10.1073/pnas.052533799
发表时间：
2002-03-19
影响因子：
11.1
作者：
Canny, G;Levy, O;Colgan, SP
通讯作者：
Colgan, SP
专门的促解决介质：感染和炎症的内源性调节剂。
DOI：
10.1038/nri.2015.4
发表时间：
2016-01
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Basil MC;Levy BD
通讯作者：
Levy BD
影响因子：
8
作者：
通讯作者：
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