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NF-κB抑制剂DHMEQ对鼻息肉成纤维细胞炎性细胞因子分泌的抑制作用

Suppression of inflammatory cytokine secretion by an NF-ĸB inhibitor DHMEQ in nasal polyps fibroblasts.

作者信息

Valera Fabiana C P, Umezawa Kazuo, Brassesco María S, Castro-Gamero Angel M, Queiroz Rosane G P, Scrideli Carlos A, Tone Luiz G, Anselmo-Lima Wilma T

机构信息

Division of Otorhinolaryngology, School of Medicine of Ribeirão Preto-University of São Paulo, São Paulo, Brazil.

出版信息

Cell Physiol Biochem. 2012;30(1):13-22. doi: 10.1159/000339042. Epub 2012 Jun 5.

Abstract

BACKGROUND

NF-ĸB is an essential transcription factor strongly associated to inflammatory response in chronic rhinosinusitis with nasal polyps (CRSwNP). DHMEQ is a NF-ĸB inhibitor that has been previously described with a greatpotential indecreasing inflammation in diseases other than CRSwNP. The aim of study isto evaluate the ability of DHMEQ to reducethe inflammatory recruiters on CRSwNP and to compare its anti-inflammatory profile as a single-agent or in association with fluticasone propionate (FP).

METHODS

nasal polyp fibroblasts were cultured in TNF-α enriched media. Cells were submitted to three different concentrations (1, 10 and 100nM) of either FP, DHMEQ or both. Inflammatory response was accessed by VCAM-1, ICAM-1 and RANTES expression (by RTQ-PCR) and protein levels by ELISA. Nuclear translocation of NF-ĸB was also evaluated.

RESULTS

both FP and DHMEQ inhibited inflammatory recruiters' production and NF-ĸB nuclear translocation. Interestingly, the anti-inflammatory effect from the association steroids plus DHMEQ was more intense than of each drug in separate.

CONCLUSION

DHMEQ seems efficient in modulating the inflammatory process in CRSwNP. The synergic anti-inflammatory effect of DHMEQ and steroids may be a promising strategy to be explored, particularly in the setting of steroid-resistant NP.

摘要

背景

核因子-κB(NF-κB)是一种重要的转录因子,与伴鼻息肉的慢性鼻-鼻窦炎(CRSwNP)的炎症反应密切相关。DHMEQ是一种NF-κB抑制剂,此前已被描述在CRSwNP以外的疾病中具有很大的抗炎潜力。本研究的目的是评估DHMEQ减少CRSwNP炎症介质的能力,并比较其作为单一药物或与丙酸氟替卡松(FP)联合使用时的抗炎特性。

方法

鼻息肉成纤维细胞在富含肿瘤坏死因子-α(TNF-α)的培养基中培养。细胞分别接受三种不同浓度(1、10和100 nM)的FP、DHMEQ或两者。通过VCAM-1、ICAM-1和RANTES表达(实时定量聚合酶链反应法)及酶联免疫吸附测定法检测蛋白水平来评估炎症反应。还评估了NF-κB的核转位。

结果

FP和DHMEQ均抑制炎症介质的产生及NF-κB核转位。有趣的是,类固醇加DHMEQ联合使用的抗炎效果比单独使用每种药物更显著。

结论

DHMEQ似乎能有效调节CRSwNP中的炎症过程。DHMEQ与类固醇的协同抗炎作用可能是一种有前景的策略,尤其在类固醇抵抗性鼻息肉的情况下。

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