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
Division of Otorhinolaryngology, School of Medicine of Ribeirão Preto-University of São Paulo, São Paulo, Brazil.
Cell Physiol Biochem. 2012;30(1):13-22. doi: 10.1159/000339042. Epub 2012 Jun 5.
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).
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.
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.
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.
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。
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。
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。
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。