Okano Mitsuhiro, Fujiwara Tazuko, Haruna Takenori, Kariya Shin, Makihara Seiichiro, Higaki Takaya, Nishizaki Kazunori
Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
J Allergy Clin Immunol. 2009 Apr;123(4):868-74.e13. doi: 10.1016/j.jaci.2009.01.047. Epub 2009 Feb 28.
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.
We sought to determine whether COX metabolism, especially prostaglandin (PG) E(2), plays a significant role in SE-induced cellular responses in nasal polyps.
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.
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. PGE(2) 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.
These results suggest that PGE(2) inhibits the pathogenesis of SEB-induced eosinophilic inflammation primarily through the EP2-mediated pathway in patients with chronic rhinosinusitis with nasal polyposis.
最近的研究表明，葡萄球菌肠毒素（SEs）、COX代谢或两者可能参与嗜酸性气道疾病的发病机制，如伴有鼻息肉的慢性鼻-鼻窦炎。
我们试图确定COX代谢，尤其是前列腺素（PG）E2，在SE诱导的鼻息肉细胞反应中是否起重要作用。
通过酶消化从鼻息肉中制备分散的鼻息肉细胞（DNPCs）。DNPCs在有或无COX抑制剂（双氯芬酸和吲哚美辛）存在的情况下与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。研究了PGE2对双氯芬酸处理的DNPCs的SEB诱导反应的影响，特别是在受体特异性方面。
DNPCs对SEB产生大量的IL-5、IL-13和RANTES。COX抑制剂显著增加了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产生变化呈显著正相关。PGE2显著且剂量依赖性地抑制双氯芬酸处理的DNPCs的SEB诱导的IL-5、IL-13和RANTES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。EP3和EP4受体选择性激动剂部分抑制这些反应，而EP1受体选择性激动剂则无此作用。有趣的是，4种EP受体选择性激动剂中的2种联合处理均显著抑制双氯芬酸处理的DNPCs的SEB诱导反应。
这些结果表明，在伴有鼻息肉的慢性鼻-鼻窦炎患者中，PGE2主要通过EP2介导的途径抑制SEB诱导的嗜酸性炎症的发病机制。
