RT Journal Article
SR Electronic
T1 MAPKAP kinase 2(MK2) expression is associated with severe asthma
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP PA4649
DO 10.1183/13993003.congress-2016.PA4649
VO 48
IS suppl 60
A1 Geoffrey Chupp
A1 Xiting Yan
A1 Vera Nezgovorova
A1 Nicole Grant
A1 Williamson Bradford
A1 Colleen Brophy
A1 Lauren Cohn
YR 2016
UL http://erj.ersjournals.com/content/48/suppl_60/PA4649.abstract
AB 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.