COX/PGE2 axis critically regulates effects of LPS on eosinophilia-associated cytokine production in nasal polyps
COX/PGE2 axis critically regulates effects of LPS on eosinophilia-associated cytokine production in nasal polyps
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DOI：
10.1111/j.1365-2222.2012.04015.x
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发表时间：
2012-08-01
影响因子：
6.1
通讯作者：
Nishizaki, K.
中科院分区：
文献类型：
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作者：
Higaki, T.;Okano, M.;Nishizaki, K.
背景 脂多糖 (LPS) 对气道嗜酸性粒细胞炎症表现出异质性影响。然而，人们对 LPS 如何调节伴有鼻息肉的慢性鼻窦炎（上呼吸道嗜酸性粒细胞炎症的一种主要形式）的发病机制知之甚少。 目的 我们试图研究 LPS 对分散性鼻息肉细胞 (DNPC) 产生细胞因子的影响。 方法 在存在或不存在 LPS 的情况下，不含葡萄球菌肠毒素 B (SEB)，然后测量上清液中 IL-5、IL-13、IL-17A 和 IFN-γ 的水平。还检查了 PGE(2) 对双氯芬酸处理的 DNPCs 的 LPS 诱导反应的影响。测量LPS诱导的PGE(2)产生以及COX-1、COX-2和微粒体PGE(2)合酶-1(m-PGES-1)的mRNA表达。结果葡萄球菌肠毒素B诱导DNPC产生IL-5、IL-13、IL-17A和IFN-γ。 SEB 刺激前用 LPS 进行预处理可抑制这些细胞因子的产生。 LPS刺激后，DNPCs的PGE(2)产生以及COX-2和m-PGES-1 mRNA的表达显着增加。在双氯芬酸存在的情况下，LPS 的抑制作用被消除。 LPS 预处理增强了 SEB 诱导的双氯芬酸处理的 DNPC 中 IL-5、IL-13 和 IL-17A 的产生，而添加 PGE(2) 则抑制了 IL-5、IL-13 和 IFN-gamma 的产生。单独的 LPS 诱导双氯芬酸处理的 DNPC 产生 IL-5、IL-13 和 IFN-γ，而添加 EP2 和 EP4 受体选择性激动剂以及 PGE(2) 本身则抑制 IL-5 和 IL-13 的产生。结论和临床相关性这些结果表明，LPS 对嗜酸性粒细胞性气道炎症的调节作用是通过 COX-2/PGE(2) 轴。就临床意义而言，患有鼻息肉的慢性鼻窦炎患者应避免不慎使用非甾体抗炎药。
Background Lipopolysaccharide (LPS) has shown heterogeneous effects on eosinophilic inflammation in airways. However, little is known about how LPS regulates pathogenesis of chronic rhinosinusitis with nasal polyps, a major form of eosinophilic inflammation in the upper airway.Objective We sought to investigate the effect of LPS on cytokine production by dispersed nasal polyp cells (DNPCs).Methods Either diclofenac-treated or untreated DNPCs were cultured with or without staphylococcal enterotoxin B (SEB) in the presence or absence of LPS, after which the levels of IL-5, IL-13, IL-17A and IFN-gamma within the supernatant were measured. The effects of PGE(2) on LPS-induced responses by diclofenac-treated DNPCs were also examined. LPS-induced PGE(2) production and mRNA expression of COX-1, COX-2 and microsomal PGE(2) synthase-1 (m-PGES-1) were measured.Results Staphylococcal enterotoxin B induced IL-5, IL-13, IL-17A and IFN-gamma production by DNPCs. Pre-treatment with LPS prior to SEB stimulation inhibited production of these cytokines. After stimulation with LPS, PGE(2) production and expression of COX-2 and m-PGES-1 mRNA by DNPCs increased significantly. In the presence of diclofenac, the suppressive effects of LPS were eliminated. LPS pre-treatment enhanced SEB-induced IL-5, IL-13 and IL-17A production in diclofenac-treated DNPCs, while addition of PGE(2) inhibited IL-5, IL-13 and IFN-gamma production. LPS alone induced IL-5, IL-13 and IFN-gamma production by diclofenac-treated DNPCs, while the addition of EP2 and EP4 receptor-selective agonists, as well as PGE(2) itself, inhibited IL-5 and IL-13 production.Conclusions and Clinical Relevance These results suggest that the regulatory effects of LPS on eosinophilic airway inflammation are controlled via the COX-2/PGE(2) axis. For clinical implications, indiscreet use of non-steroidal anti-inflammatory drugs should be avoided in patients with chronic rhinosinusitis with nasal polyps.