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

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Androstadienes / pharmacology
  • Anti-Inflammatory Agents / pharmacology
  • Benzamides / pharmacology*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Chemokine CCL5 / genetics
  • Chemokine CCL5 / metabolism
  • Cyclohexanones / pharmacology*
  • Cytokines / metabolism*
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism*
  • Fluticasone
  • Gene Expression / drug effects
  • Humans
  • Inflammation Mediators / metabolism
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Nasal Polyps / pathology*
  • Rhinitis / pathology
  • Sinusitis / pathology
  • Tumor Necrosis Factor-alpha / pharmacology
  • Vascular Cell Adhesion Molecule-1 / genetics
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Androstadienes
  • Anti-Inflammatory Agents
  • Benzamides
  • CCL5 protein, human
  • Chemokine CCL5
  • Cyclohexanones
  • Cytokines
  • Inflammation Mediators
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • dehydroxymethylepoxyquinomicin
  • Intercellular Adhesion Molecule-1
  • Fluticasone