Title: Increased Phosphorylated p38 Mitogen Activated Protein Kinase in COPD

The p38 Mitogen Activated Protein Kinase (MAPK) pathway is upregulated in COPD. To date dual-labelling to identify cell-type specific presence of phosphorylated (phospho-) p38 MAPK has not been carried out. Phospho-p38 MAPK was quantified in a variety of cell types in the lung tissue of 20 COPD patients, 12 smokers and 12 non-smokers using immunohistochemistry. Paired blood and sputum neutrophils (n=7 COPD), and CD8 and epithelial cells (n=3 COPD) were cultured with a p38 MAPK inhibitor. Supernatant TNFα, CXCL8 levels were analysed by ELISA. Sputum and blood neutrophil cytospins were analysed for phospho-p38 MAPK. Phospho-p38 MAPK was increased in bronchial epithelial cells, macrophages and CD20+ and CD8+ lymphocytes in COPD lungs. Sputum and lung tissue neutrophils were devoid of phospho-p38 in all patient groups. The p38 MAPK inhibitor SB100 attenuated pro-inflammatory mediator release in COPD lung CD8 cells and airway epithelia but there was no effect on COPD sputum neutrophils. Our data indicates cell specific anti-inflammatory effects of p38 MAPK inhibition in the lung.