Suppression of Inflammatory Cytokine Secretion by an NF-kappa B Inhibitor DHMEQ in Nasal Polyps Fibroblasts

Background: NF-kappa B is an essential transcription factor strongly associated to inflammatory response in chronic rhinosinusitis with nasal polyps (CRSwNP). DHMEQ is a NF-kappa B 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-alpha 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-kappa B was also evaluated. Results: both FP and DHMEQ inhibited inflammatory recruiters' production and NF-kappa B 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. Copyright (c) 2012 S. Karger AG, BaselFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)IRBUniv São Paulo, Sch Med Ribeirao Preto, Div Otorhinolaryngol, São Paulo, BrazilKeio Univ, Fac Sci & Technol, Dept Appl Chem Yokohama, Keio, JapanUniv São Paulo, Sch Med Ribeirao Preto, Dept Pediat, São Paulo, BrazilUniv São Paulo, Sch Med Ribeirao Preto, Dept Genet, São Paulo, BrazilFAPESP: 07/50359-4IRB: 4374/2007Web of Scienc