title: Suppression of inflammatory cytokine secretion by an NF-ĸB inhibitor DHMEQ in nasal polyps fibroblasts.
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.
  
  
  CONCLUSIONS
  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.
authors: Division of Otorhinolaryngology, School of Medicine of Ribeirão Preto-University of São Paulo, São Paulo, Brazil. facpvalera@fmrp.usp.br
authors: Fabiana C P
authors: FC
authors: Valera
authors: Kazuo
authors: K
authors: Umezawa
authors: María S
authors: MS
authors: Brassesco
authors: Angel M
authors: AM
authors: Castro-Gamero
authors: Rosane G P
authors: RG
authors: Queiroz
authors: Carlos A
authors: CA
authors: Scrideli
authors: Luiz G
authors: LG
authors: Tone
authors: Wilma T
authors: WT
authors: Anselmo-Lima
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000730:Androstadienes / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D003512:Cyclohexanones / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D000068298:Fluticasone; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009298:Nasal Polyps / Q000473:pathology*; D012220:Rhinitis / Q000473:pathology; D012852:Sinusitis / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D001549:Benzamides; C483024:CCL5 protein, human; D018946:Chemokine CCL5; D003512:Cyclohexanones; D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C464444:dehydroxymethylepoxyquinomicin; D018799:Intercellular Adhesion Molecule-1; D000068298:Fluticasone