TY - JOUR T1 - MAPKAP kinase 2(MK2) expression is associated with severe asthma JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2016.PA4649 VL - 48 IS - suppl 60 SP - PA4649 AU - Geoffrey Chupp AU - Xiting Yan AU - Vera Nezgovorova AU - Nicole Grant AU - Williamson Bradford AU - Colleen Brophy AU - Lauren Cohn Y1 - 2016/09/01 UR - http://erj.ersjournals.com/content/48/suppl_60/PA4649.abstract N2 - Introduction: The p38 Mitogen-Activated Protein Kinase pathway is dysregulated in asthma. MK2 is a p38 terminal kinase that regulates multiple asthma relevant genes(e.g. ALOX5, TNF-a, IL-6, dendritic cell Toll-like receptors), but its role in human asthma is unknown. We hypothesized MK2 expression is increased in asthma.Methods: Whole transcriptome gene expression profiles in sputum and blood were measured(Affymetrix ST 1.0) from 112 asthmatics and 12 controls. MK2 gene expression was correlated with clinical, physiologic and inflammatory disease characteristics.Results: Sputum MK2 gene expression was increased in asthmatics vs. controls(p=0.04) and correlated positively with lifetime hospitalizations(p=0.03) and Severe Asthma Research Program(SARP) cluster designation, and negatively with serum IgE levels(r=-0.28,p<0.001), and pre- and post-bronchodilator FEV1(r=-0.23, p=0.02 and r=-0.21, p=0.04, respectively). Positive correlations were seen with mucus protein levels of IL-1b(r=0.33,p=0.01), IL-1R(r=0.36,p<0.01), MCSF(r=0.29,p=0.03) and chitinase activity(r=0.32, p=0.02). Mucus inflammatory cell concentrations and % neutrophils tended to correlate with sputum MK2 gene expression(r=0.17,p=0.09 and r=0.17,p<0.1). Blood MK2 gene expression demonstrated similar associations. Sputum MK2 gene expression analysis of 61 genes (MetaCore) correlated with ERK1, ERK1/2 and IL-15 genes.Conclusions: Sputum MK2 gene expression is significantly elevated in asthma, associated with poor lung function, neutrophilic inflammation and increased sputum chitinase activity. These data suggest MK2 mediates airway inflammation in asthma, particularly in severe phenotypes of disease, and warrants investigation as a therapeutic target. ER -