TY - JOUR T1 - Late-breaking abstract: Epigenetic inhibition of proliferation and inflammation in airway epithelium JF - European Respiratory Journal JO - Eur Respir J VL - 44 IS - Suppl 58 SP - 2911 AU - Bianca van Groen AU - Peter Brook AU - Ian Adcock AU - Andrew Durham Y1 - 2014/09/01 UR - http://erj.ersjournals.com/content/44/Suppl_58/2911.abstract N2 - BackgroundEpigenetic mechanisms such as histone acetylation and methylation are key regulators of gene regulation and considered to be important in chronic lung diseases such as fibrosis, lung cancer, asthma and COPD. Recently chemical probes have been developed that specifically inhibit the functional effects of histone methylation and acetylation tags deposited by histone methyltransferases (UNC0638, UNC0642, UNC1999, GSK343 and PFI2), histone demethylases (KDM) (GSKJ1, GSKJ4) or bromodomain containing proteins (BCP) (JQ1+, bromosporine, GSK2801, SGCBP30). We investigated the ability of these inhibitors to modulate proliferation and inflammation in human airway epithelial cells.MethodsPrimary human normal human bronchial epithelial cells (NHBE) and BEAS2B were treated with the probes (0-1000nM for BCP probes, 0-360uM for KDM probes) and/or IL-1B (1ng/ml). Cell viability (MTT), proliferation (BrdU) and inflammation (IL-6 ELISA) were measured.ResultsIn BEAS2B cells KDM and BCP inhibitors significantly reduced proliferation by 40-100% at concentrations (<1mM for BCP probes, <0.36mM for KDM probes) that did not affect cell viability. Only the BET inhibitors JQ1+ and bromosporine significantly decreased IL-1B induced IL-6 release by 80-90%. Similar results were observed in NHBE cells.DiscussionOur results indicate that both histone (de)methylase and BCP protein functions are important in human airway epithelial cell proliferation. However, only BCPs are essential for the regulation of the inflammatory response in these cells. Pharmacological targeting of epigenetic writers and readers will aid understanding of epithelial cell hyper proliferation (fibrosis and lung cancer) and inflammation (asthma and COPD). ER -