Increased phosphorylated p38 mitogen-activated protein kinase in COPD lungs.
The p38 mitogen-activated protein kinase (MAPK) pathway is upregulated in chronic obstructive pulmonary disease (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 nonsmokers using immunohistochemistry. Paired blood and sputum neutrophils (from seven subjects with COPD), and CD8 and epithelial cells (from three subjects with COPD) were cultured with a p38 MAPK inhibitor. Supernatant tumour necrosis factor-α and 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 indicate cell-specific anti-inflammatory effects of p38 MAPK inhibition in the lung.
University of Manchester, NIHR Translational Research Facility, University Hospital of South Manchester, Manchester, UK.
Kate
K
Gaffey
Sophie
S
Reynolds
Jonathan
J
Plumb
Manminder
M
Kaur
Dave
D
Singh
D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D002478:Cells, Cultured / Q000166:cytology; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000201:enzymology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D008264:Macrophages / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism; D010766:Phosphorylation; D029424:Pulmonary Disease, Chronic Obstructive / Q000201:enzymology* / Q000503:physiopathology*; D012907:Smoking; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D016207:Cytokines; D048051:p38 Mitogen-Activated Protein Kinases