TY - JOUR T1 - Promotional effect of 27-hydroxycholesterol in the release of matrix metalloproteinases by lung fibroblasts JF - European Respiratory Journal JO - Eur Respir J VL - 42 IS - Suppl 57 SP - P3882 AU - Takashi Kikuchi AU - Hisatoshi Sugiura AU - Tomohiro Ichikawa AU - Akira Koarai AU - Masakazu Ichinose Y1 - 2013/09/01 UR - http://erj.ersjournals.com/content/42/Suppl_57/P3882.abstract N2 - (Rationale) 27-Hydroxycholesterol (27-OHC) has been reported to have inflammatory effects on several types of cells such as endothelial cells and neuronal cells. Recent studies also have demonstrated that 27-OHC was related to the pathogenesis of some degenerative disorders such as Alzheimer’s disease and age-related macular degeneration. Previously, we reported that 27-OHC increased in the airways of chronic obstructive pulmonary disease (COPD) and was involved in airway fibrosis. However, the effect of 27-OHC in the release of matrix metalloproteinases (MMPs) which are key mediators in the pathogenesis of COPD remains unknown. In the current study, we examined the possible role of 27-OHC in the release of MMPs by lung fibroblasts.(Methods) We treated human fetal lung fibroblasts (HFL-1) with various concentrations of 27-OHC. The release of MMP-2 and MMP-9 were assessed by gelatin zymography. To explore its signal transduction, we evaluated the transforming growth factor (TGF)-β1 release by ELISA and the translocation of nuclear factor-kappa B (NF-κB) p65 by western blot.(Results) 27-OHC augmented the release of MMP-2 and MMP-9 through the translocation of NF-κB p65 and subsequent TGF-β1 up-regulation. Caffeic acid phenethyl ester (CAPE) which is a novel NF-κB inhibitor inhibited the 27-OHC-augmented total TGF-β1 release and neutralizing anti-TGF-β antibody inhibited the 27-OHC-augmented MMPs release.(Conclusion) These results suggest that 27-OHC has the promotional effect in the release of matrix metalloproteinases and may be involved in the pathogenesis of COPD in this regard. ER -