Brain Korea 21 Plus for Biomedical Science, Korea University College of Medicine, Seoul, Korea. ; Institute for Medical Devices Clinical Trial Center, Guro Hospital, Korea University, Seoul, Korea.
Brain Korea 21 Plus for Biomedical Science, Korea University College of Medicine, Seoul, Korea.
Allergy Asthma Immunol Res. 2014 Sep;6(5):449-57. doi: 10.4168/aair.2014.6.5.449. Epub 2014 Jun 4.
Interleukin 6 (IL-6) and IL-8 participate in the pathogenesis of chronic rhinosinusitis with nasal polyps, and their levels are increased by prostaglandin E2 (PGE2) in different cell types. The purposes of this study were to determine whether PGE2 has any effect on the increase in the levels of IL-6 and IL-8 in nasal polyp-derived fibroblasts (NPDFs) and subsequently investigate the possible mechanism of this effect.
Different concentrations of PGE2 were used to stimulate NPDFs at different time intervals. NPDFs were treated with agonists and antagonists of E prostanoid (EP) receptors. To determine the signaling pathway for the expression of PGE2-induced IL-6 and IL-8, PGE2 was treated with Akt and NF-κB inhibitors in NPDFs. Reverse transcription-polymerase chain reaction for IL-6 and IL-8 mRNAs was performed. IL-6 and IL-8 levels were measured byenzyme-linked immunosorbent assay (ELISA). The activation of Akt and NF-κB was evaluated by western blot analysis.
PGE2 significantly increased the mRNA and protein expression levels of IL-6 and IL-8 in NPDFs. The EP2 and EP4 agonists and antagonists induced and inhibited IL-6 expression. However, the EP4 agonist and antagonist were only observed to induce and inhibit IL-8 expression level. The Akt and NF-κB inhibitors significantly blocked PGE2-induced expression of IL-6 and IL-8.
PGE2 increases IL-6 expression via EP2 and EP4 receptors, and IL-8 expression via the EP4 receptor in NPDFs. It also activates the Akt and NF-κB signal pathways for the production of IL-6 and IL-8 in NPDFs. These results suggest that signaling pathway for IL-6 and IL-8 expression induced by PGE2 might be a useful therapeutic target for the treatment of nasal polyposis.
白细胞介素 6（IL-6）和 IL-8 参与鼻息肉慢性鼻窦炎的发病机制，其在不同细胞类型中的水平可被前列腺素 E2（PGE2）升高。本研究旨在确定 PGE2 是否对鼻息肉衍生成纤维细胞（NPDFs）中 IL-6 和 IL-8 水平的升高有任何影响，并随后研究该影响的可能机制。
不同浓度的 PGE2 在不同时间间隔刺激 NPDFs。用 E 前列腺素（EP）受体激动剂和拮抗剂处理 NPDFs。为了确定 PGE2 诱导的 IL-6 和 IL-8 表达的信号通路，用 Akt 和 NF-κB 抑制剂处理 NPDFs 中的 PGE2。进行 IL-6 和 IL-8 mRNA 的逆转录-聚合酶链反应。通过酶联免疫吸附试验（ELISA）测量 IL-6 和 IL-8 水平。通过 Western blot 分析评估 Akt 和 NF-κB 的激活。
PGE2 显著增加了 NPDFs 中 IL-6 和 IL-8 的 mRNA 和蛋白表达水平。EP2 和 EP4 激动剂和拮抗剂诱导和抑制了 IL-6 的表达。然而，仅观察到 EP4 激动剂和拮抗剂诱导和抑制了 IL-8 的表达水平。Akt 和 NF-κB 抑制剂显著阻断了 PGE2 诱导的 IL-6 和 IL-8 表达。
PGE2 通过 EP2 和 EP4 受体增加 NPDFs 中 IL-6 的表达，通过 EP4 受体增加 IL-8 的表达。它还激活了 Akt 和 NF-κB 信号通路，促进了 NPDFs 中 IL-6 和 IL-8 的产生。这些结果表明，PGE2 诱导的 IL-6 和 IL-8 表达的信号通路可能是治疗鼻息肉的一个有前途的治疗靶点。
