Lipoxin A4 and aspirin-triggered 15-epi-LXA4 inhibit tumor necrosis factor-α-initiated neutrophil responses and trafficking:: novel regulators of a cytokine-chemokine axis relevant to periodontal diseases
Lipoxin A4 and aspirin-triggered 15-epi-LXA4 inhibit tumor necrosis factor-α-initiated neutrophil responses and trafficking:: novel regulators of a cytokine-chemokine axis relevant to periodontal diseases
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DOI：
10.1111/j.1600-0765.1999.tb02268.x
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发表时间：
1999-10-01
影响因子：
3.5
通讯作者：
Serhan, CN
中科院分区：
文献类型：
--
作者：
Pouliot, M;Serhan, CN
研究了脂素A(4) （LXA(4)）和阿斯匹林触发的脂素（ATL）在体外和体内对肿瘤坏死因子（TNF α）启动的中性粒细胞（PMN）反应的影响，使用代谢更稳定的LX类似物。在纳摩尔水平，LXA(4)和ATL类似物15 R/ s -甲基LXA(4)分别阻断体外分离的人PMN对TNF α刺激的IL-1 β的释放。这些LXA(4)- atl作用具有时间和浓度依赖性。TNF α诱导的IL-1 β基因表达也受到15r / s -甲基- lxa的调控(4)。此外，在小鼠气袋中添加15r / s -甲基- lxa(4)可显著抑制TNF α刺激的白细胞在体内的运输，并改变巨噬细胞炎症肽-2和IL-1 β的外观，同时刺激气袋渗出物中的IL-4。这些来自体外和体内实验的发现表明，LXA(4)和ATL都是TNF α导向的中性粒细胞作用的调节剂，刺激渗出液中的IL-4，从而调节在牙周病发病机制中起重要作用的介质。
The impact of lipoxin A(4) (LXA(4)) and aspirin-triggered-lipoxins (ATL) was investigated in tumor necrosis factor (TNF alpha)-initiated neutrophil (PMN) responses in vitro and in vivo using LX analogs that are metabolically more stable. At nanomolar levels, the LXA(4) and ATL analog 15 R/S-methyl-LXA(4) each blocked TNF alpha-stimulated IL-1 beta release by isolated human PMN in vitro. These LXA(4)-ATL actions were time- and concentration-dependent. The TNF alpha-induced IL-1 beta gene expression was also regulated by 15 R/S-methyl-LXA(4). In addition, 15 R/S-methyl-LXA(4) added to murine air pouches dramatically inhibited TNF alpha-stimulated leukocyte trafficking in vivo, as well as altered the appearance of both macrophage inflammatory peptide-2 and IL-1 beta and concomitantly stimulated IL-4 in pouch exudates. These findings from in vitro and in vivo experiments indicate that both LXA(4) and ATL are regulators of TNF alpha-directed neutrophil actions and stimulate IL-4 in exudates and thus regulate mediators that are held to play an important role in the pathogenesis of periodontal disease.