Effects of a novel nonantibiotic macrolide, EM900, on cytokine and mucin gene expression in a human airway epithelial cell line.
Effects of a novel nonantibiotic macrolide, EM900, on cytokine and mucin gene expression in a human airway epithelial cell line.
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新型非抗生素大环内酯 EM900 对人气道上皮细胞系细胞因子和粘蛋白基因表达的影响。
DOI：
10.1159/000334339
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发表时间：
2011
期刊：
影响因子：
3.1
通讯作者：
Takeuchi K.
中科院分区：
文献类型：
--
作者：
Otsu K;Ishinaga H;Suzuki S;Sugawara A;Sunazuka T;Omura S;Jono H;Takeuchi K.
背景/目的：长期大环内酯类药物治疗是慢性鼻窦炎和弥漫性泛细支气管炎的有效治疗方法。然而，长期使用大环内酯类药物可能会促进耐药性细菌的生长;因此，需要开发无抗菌作用的大环内酯类药物。新的红霉素（EM）衍生物（8 R，9 S）-8，9-二氢-6，9-环氧-8，9-脱水假红霉素A（EM 900）不具有抗菌作用。方法：为了确定EM 900是否诱导临床相关的抗炎反应并抑制人气道上皮细胞中的粘蛋白基因表达，我们评估了EM 900对A549细胞中IL-1β诱导的炎性细胞因子和HM 3-MUC 5AC细胞中MUC 5AC基因表达的影响。我们还研究了EM 900对IL-1β诱导的NF-κ B活化的影响。结果：EM和EM 900均能抑制IL-1β诱导的A549细胞IL-8的表达。EM 900还能抑制IL-1β诱导的A549细胞IL-1β和TNF-α的表达。EM 900可抑制IL-1β诱导的HM 3-MUC 5AC细胞MUC 5AC表达。EM和EM 900均能抑制IL-1β诱导的A549细胞NF-κ B的活化。结论：EM 900能抑制IL-1β诱导的人气道上皮细胞炎症因子的产生和MUC 5AC基因的表达，其作用可能是通过抑制NF-κ B的活化而实现的。
Background/Aims:Long-term macrolide therapy is an effective treatment for chronic sinusitis and diffuse panbronchiolitis. However, long-term use of macrolides may promote the growth of drug-resistant bacteria; therefore, development of macrolides with no antibacterial action is desirable. A new erythromycin (EM) derivative, (8R,9S)- 8,9-dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin A (EM900), does not possess antibacterial action.Methods:To determine whether EM900 induced a clinically relevant anti-inflammatory response and repressed mucin gene expression in cells derived from human airway epithelia, we assessed the effects of EM900 on IL-1β-induced inflammatory cytokines in A549 cells andMUC5ACgene expression in HM3-MUC5AC cells. We also investigated the effects of EM900 on IL-1β-induced NF-ĸB activation. We performed reporter gene assays and quantitative PCR in A549 and HM3-MUC5AC cells.Results:Both EM and EM900 suppressed IL-1β-inducedIL-8expression in A549 cells. EM900 also suppressed IL-1β-inducedIL-1β andTNF-α expression in A549 cells. EM900 inhibited IL-1β-inducedMUC5ACexpression in HM3-MUC5AC cells. Both EM and EM900 suppressed IL-1β-induced NF-ĸB activation in A549 cells.Conclusion:This study demonstrated that EM900 suppressed the induction of inflammatory cytokines andMUC5ACgene expression in cells derived from human airway epithelia, and our findings indicate that these effects may be mediated by the suppression of NF-ĸB activation.