Prostaglandin E2 suppresses staphylococcal enterotoxin-induced eosinophilia-associated cellular responses dominantly through an E-prostanoid 2-mediated pathway in nasal polyps
Prostaglandin E2 suppresses staphylococcal enterotoxin-induced eosinophilia-associated cellular responses dominantly through an E-prostanoid 2-mediated pathway in nasal polyps
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DOI：
10.1016/j.jaci.2009.01.047
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发表时间：
2009-04-01
影响因子：
14.2
通讯作者：
Nishizaki, Kazunori
中科院分区：
文献类型：
--
作者：
Okano, Mitsuhiro;Fujiwara, Tazuko;Nishizaki, Kazunori
背景资料：近年来的研究表明，葡萄球菌肠毒素（SE）、考克斯代谢或两者共同参与了嗜酸性粒细胞性气道疾病的发病机制，如慢性鼻窦炎伴鼻息肉病。目的：我们试图确定考克斯代谢，尤其是前列腺素（PG）E-2，是否在SE诱导的鼻息肉细胞反应中起重要作用。采用酶消化法从鼻息肉组织中制备鼻息肉细胞。在存在或不存在考克斯抑制剂（双氯芬酸和吲哚美辛）的情况下，将DNPC与SEB一起培养72小时;然后测量上清液中IL-5、IL-13、RANTES和嗜酸性粒细胞趋化因子的水平。PGE（2）对SEB诱导的DNPC反应的影响被检测，特别是在受体特异性方面。考克斯抑制剂显著增加这些细胞因子的产生。局部嗜酸性粒细胞增多的程度与双氯芬酸治疗诱导的IL-5产生的变化显著正相关。PGE 2显著地且剂量依赖性地抑制SEB诱导的IL-5、IL-13和RANTES由diclactac-treated DNPCs产生。E-前列腺素（EP）2受体选择性激动剂强烈抑制所有3种细胞因子的产生。EP 3和EP 4受体选择性激动剂部分抑制这些反应，而EP 1受体选择性激动剂没有。有趣的是，所有的4 EP受体选择性激动剂与2的联合治疗显着抑制SEB诱导的反应由diclethac-treated DNPCs.Conclusions：这些结果表明，前列腺素E2抑制SEB诱导的嗜酸性粒细胞炎症的发病机制，主要是通过EP 2介导的途径，在慢性鼻窦炎鼻息肉病患者。（J Allergy Clin Immunol 2009;123：868-74.）
Background: Recent investigations have revealed that staphylococcal enterotoxins (SEs), COX metabolism, or both might participate in the pathogenesis of eosinophilic airway diseases, such as chronic rhinosinusitis with nasal polyposis.Objective: We sought to determine whether COX metabolism, especially prostaglandin (PG) E-2, plays a significant role in SE-induced cellular responses in nasal polyps.Methods: Dispersed nasal polyp cells (DNPCs) were prepared from nasal polyps by means of enzymatic digestion. DNPCs were cultured with SEB in the presence or absence of COX inhibitors (diclofenac and indomethacin) for 72 hours; then the levels of IL-5, IL-13, RANTES, and eotaxin in the supernatants were measured. The effect of PGE(2) on SEB-induced responses by diclofenac-treated DNPCs was examined, especially in terms of receptor specificity.Results: DNPCs produced significant amounts of IL-5, IL-13, and RANTES in response to SEB. COX inhibitors significantly increased the production of these cytokines. The degree of local eosinophilia was significantly and positively correlated with the changes in IL-5 production induced by diclofenac treatment. PGE2 significantly and dose-dependently inhibited SEB-induced IL-5, IL-13, and RANTES production by diclofenac-treated DNPCs. E-prostanoid (EP) 2 receptor-selective agonist strongly inhibited the production of all 3 cytokines. EP3 and EP4 receptor-selective agonists partially suppressed these responses, whereas EP1 receptor-selective agonist did not. Interestingly, all of the combined treatments with 2 of the 4 EP receptor-selective agonists significantly inhibited the SEB-induced responses by diclofenac-treated DNPCs.Conclusions: These results suggest that PGE2 inhibits the pathogenesis of SEB-induced eosinophilic inflammation primarily through the EP2-mediated pathway in patients with chronic rhinosinusitis with nasal polyposis. (J Allergy Clin Immunol 2009;123:868-74.)